WorldWideScience

Sample records for reverse engineering biological

  1. Reverse engineering development: Crosstalk opportunities between developmental biology and tissue engineering.

    Science.gov (United States)

    Marcucio, Ralph S; Qin, Ling; Alsberg, Eben; Boerckel, Joel D

    2017-11-01

    The fields of developmental biology and tissue engineering have been revolutionized in recent years by technological advancements, expanded understanding, and biomaterials design, leading to the emerging paradigm of "developmental" or "biomimetic" tissue engineering. While developmental biology and tissue engineering have long overlapping histories, the fields have largely diverged in recent years at the same time that crosstalk opportunities for mutual benefit are more salient than ever. In this perspective article, we will use musculoskeletal development and tissue engineering as a platform on which to discuss these emerging crosstalk opportunities and will present our opinions on the bright future of these overlapping spheres of influence. The multicellular programs that control musculoskeletal development are rapidly becoming clarified, represented by shifting paradigms in our understanding of cellular function, identity, and lineage specification during development. Simultaneously, advancements in bioartificial matrices that replicate the biochemical, microstructural, and mechanical properties of developing tissues present new tools and approaches for recapitulating development in tissue engineering. Here, we introduce concepts and experimental approaches in musculoskeletal developmental biology and biomaterials design and discuss applications in tissue engineering as well as opportunities for tissue engineering approaches to inform our understanding of fundamental biology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2356-2368, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  2. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  3. Reverse engineering biological networks :applications in immune responses to bio-toxins.

    Energy Technology Data Exchange (ETDEWEB)

    Martino, Anthony A.; Sinclair, Michael B.; Davidson, George S.; Haaland, David Michael; Timlin, Jerilyn Ann; Thomas, Edward Victor; Slepoy, Alexander; Zhang, Zhaoduo; May, Elebeoba Eni; Martin, Shawn Bryan; Faulon, Jean-Loup Michel

    2005-12-01

    Our aim is to determine the network of events, or the regulatory network, that defines an immune response to a bio-toxin. As a model system, we are studying T cell regulatory network triggered through tyrosine kinase receptor activation using a combination of pathway stimulation and time-series microarray experiments. Our approach is composed of five steps (1) microarray experiments and data error analysis, (2) data clustering, (3) data smoothing and discretization, (4) network reverse engineering, and (5) network dynamics analysis and fingerprint identification. The technological outcome of this study is a suite of experimental protocols and computational tools that reverse engineer regulatory networks provided gene expression data. The practical biological outcome of this work is an immune response fingerprint in terms of gene expression levels. Inferring regulatory networks from microarray data is a new field of investigation that is no more than five years old. To the best of our knowledge, this work is the first attempt that integrates experiments, error analyses, data clustering, inference, and network analysis to solve a practical problem. Our systematic approach of counting, enumeration, and sampling networks matching experimental data is new to the field of network reverse engineering. The resulting mathematical analyses and computational tools lead to new results on their own and should be useful to others who analyze and infer networks.

  4. Evolutionary optimization with data collocation for reverse engineering of biological networks.

    Science.gov (United States)

    Tsai, Kuan-Yao; Wang, Feng-Sheng

    2005-04-01

    Modern experimental biology is moving away from analyses of single elements to whole-organism measurements. Such measured time-course data contain a wealth of information about the structure and dynamic of the pathway or network. The dynamic modeling of the whole systems is formulated as a reverse problem that requires a well-suited mathematical model and a very efficient computational method to identify the model structure and parameters. Numerical integration for differential equations and finding global parameter values are still two major challenges in this field of the parameter estimation of nonlinear dynamic biological systems. We compare three techniques of parameter estimation for nonlinear dynamic biological systems. In the proposed scheme, the modified collocation method is applied to convert the differential equations to the system of algebraic equations. The observed time-course data are then substituted into the algebraic system equations to decouple system interactions in order to obtain the approximate model profiles. Hybrid differential evolution (HDE) with population size of five is able to find a global solution. The method is not only suited for parameter estimation but also can be applied for structure identification. The solution obtained by HDE is then used as the starting point for a local search method to yield the refined estimates.

  5. Electrochemical reverse engineering: A systems-level tool to probe the redox-based molecular communication of biology.

    Science.gov (United States)

    Li, Jinyang; Liu, Yi; Kim, Eunkyoung; March, John C; Bentley, William E; Payne, Gregory F

    2017-04-01

    The intestine is the site of digestion and forms a critical interface between the host and the outside world. This interface is composed of host epithelium and a complex microbiota which is "connected" through an extensive web of chemical and biological interactions that determine the balance between health and disease for the host. This biology and the associated chemical dialogues occur within a context of a steep oxygen gradient that provides the driving force for a variety of reduction and oxidation (redox) reactions. While some redox couples (e.g., catecholics) can spontaneously exchange electrons, many others are kinetically "insulated" (e.g., biothiols) allowing the biology to set and control their redox states far from equilibrium. It is well known that within cells, such non-equilibrated redox couples are poised to transfer electrons to perform reactions essential to immune defense (e.g., transfer from NADH to O 2 for reactive oxygen species, ROS, generation) and protection from such oxidative stresses (e.g., glutathione-based reduction of ROS). More recently, it has been recognized that some of these redox-active species (e.g., H 2 O 2 ) cross membranes and diffuse into the extracellular environment including lumen to transmit redox information that is received by atomically-specific receptors (e.g., cysteine-based sulfur switches) that regulate biological functions. Thus, redox has emerged as an important modality in the chemical signaling that occurs in the intestine and there have been emerging efforts to develop the experimental tools needed to probe this modality. We suggest that electrochemistry provides a unique tool to experimentally probe redox interactions at a systems level. Importantly, electrochemistry offers the potential to enlist the extensive theories established in signal processing in an effort to "reverse engineer" the molecular communication occurring in this complex biological system. Here, we review our efforts to develop this

  6. A reverse engineering approach to optimize experiments for the construction of biological regulatory networks.

    Science.gov (United States)

    Zhang, Xiaomeng; Shao, Bin; Wu, Yangle; Qi, Ouyang

    2013-01-01

    One of the major objectives in systems biology is to understand the relation between the topological structures and the dynamics of biological regulatory networks. In this context, various mathematical tools have been developed to deduct structures of regulatory networks from microarray expression data. In general, from a single data set, one cannot deduct the whole network structure; additional expression data are usually needed. Thus how to design a microarray expression experiment in order to get the most information is a practical problem in systems biology. Here we propose three methods, namely, maximum distance method, trajectory entropy method, and sampling method, to derive the optimal initial conditions for experiments. The performance of these methods is tested and evaluated in three well-known regulatory networks (budding yeast cell cycle, fission yeast cell cycle, and E. coli. SOS network). Based on the evaluation, we propose an efficient strategy for the design of microarray expression experiments.

  7. Reverse engineering for quality systems

    International Nuclear Information System (INIS)

    Nolan, A.J.

    1995-01-01

    When the age of software engineering began, many companies were faced with a problem of how to support the older, pre-software-engineering, programs. The techniques of reverse engineering and re-engineering were developed to bridge the gap between the past and the present. Although reverse engineering can be used for generating missing documentation, it can also be used as a means to demonstrate quality in these older programs. This paper presents, in the form of a case study, how Rolls-Royce and Associates Limited addressed the quality issues of reverse engineering and re-engineering. (author)

  8. Reverse engineering of RFID devices

    NARCIS (Netherlands)

    Bokslag, W.

    2015-01-01

    This paper discusses the relevance and potential impact of both RFID and reverse engineering of RFID technology, followed by a discussion of common protocols and internals of RFID technology. The focus of the paper is on providing an overview of the different approaches to reverse engineering RFID

  9. MODELS OF PROJECT REVERSE ENGINEERING

    Directory of Open Access Journals (Sweden)

    Віктор Володимирович ІВАНОВ

    2017-03-01

    Full Text Available Reverse engineering decided important scientific and technical problems of increasing the cost of the existing technical product by transforming it into a product with other features or design. Search ideas of the new application of existing products on the base of heuristic analysis were created. The concept of reverse engineering and its division into three types: conceptual, aggregate and complete was expanded. The use of heuristic methods for reverse engineering concept was showed. The modification model of Reverse engineering based on the model of РМВОК was developed. Our model includes two new phases: identification and transformation. At the identification phase, technical control is made. At the transformation phase, search heuristic idea of the new applied existing technical product was made. The model of execution phase that included heuristic methods, metrological equipment, and CAD/CAM/CAE program complex was created. The model that connected economic indicators of reverse engineering project was developed.

  10. MORE: mixed optimization for reverse engineering--an application to modeling biological networks response via sparse systems of nonlinear differential equations.

    Science.gov (United States)

    Sambo, Francesco; de Oca, Marco A Montes; Di Camillo, Barbara; Toffolo, Gianna; Stützle, Thomas

    2012-01-01

    Reverse engineering is the problem of inferring the structure of a network of interactions between biological variables from a set of observations. In this paper, we propose an optimization algorithm, called MORE, for the reverse engineering of biological networks from time series data. The model inferred by MORE is a sparse system of nonlinear differential equations, complex enough to realistically describe the dynamics of a biological system. MORE tackles separately the discrete component of the problem, the determination of the biological network topology, and the continuous component of the problem, the strength of the interactions. This approach allows us both to enforce system sparsity, by globally constraining the number of edges, and to integrate a priori information about the structure of the underlying interaction network. Experimental results on simulated and real-world networks show that the mixed discrete/continuous optimization approach of MORE significantly outperforms standard continuous optimization and that MORE is competitive with the state of the art in terms of accuracy of the inferred networks.

  11. Malware analysis and reverse engineering

    OpenAIRE

    Šváb, Martin

    2014-01-01

    Focus of this thesis is reverse engineering in information technology closely linked with the malware analysis. It explains fundamentals of IA-32 processors architecture and basics of operating system Microsoft Windows. Main part of this thesis is dedicated to the malware analysis, including description of creating a tool for simplification of static part of the analysis. In Conclusion various approaches to the malware analysis, which were described in previous part of the thesis, are practic...

  12. Reverse engineering of integrated circuits

    Science.gov (United States)

    Chisholm, Gregory H.; Eckmann, Steven T.; Lain, Christopher M.; Veroff, Robert L.

    2003-01-01

    Software and a method therein to analyze circuits. The software comprises several tools, each of which perform particular functions in the Reverse Engineering process. The analyst, through a standard interface, directs each tool to the portion of the task to which it is most well suited, rendering previously intractable problems solvable. The tools are generally used iteratively to produce a successively more abstract picture of a circuit, about which incomplete a priori knowledge exists.

  13. Repeatable Reverse Engineering with PANDA

    Science.gov (United States)

    2015-12-08

    necessary layout information for the Android 2.3 and 4.2 SDK kernels. See Section IV-C for an example of the kind of deep reverse engineering of Android apps ...code re-use and simplifying complex analysis development. We demonstrate PANDA’s effectiveness via a number of use cases, including enabling an old but...continue to function. 2) Identify critical vulnerabilities . 3) Understand the true purpose and actions of code. It is common for legacy code to stop

  14. Combining chemoinformatics with bioinformatics: in silico prediction of bacterial flavor-forming pathways by a chemical systems biology approach "reverse pathway engineering".

    Science.gov (United States)

    Liu, Mengjin; Bienfait, Bruno; Sacher, Oliver; Gasteiger, Johann; Siezen, Roland J; Nauta, Arjen; Geurts, Jan M W

    2014-01-01

    The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology.

  15. Engineering a Biological Revolution.

    Science.gov (United States)

    Matheson, Susan

    2017-01-26

    The new field of synthetic biology promises to change health care, computer technology, the production of biofuels, and more. Students participating in the International Genetically Engineered Machine (iGEM) competition are on the front lines of this revolution. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Multiplexed Engineering in Biology.

    Science.gov (United States)

    Rogers, Jameson K; Church, George M

    2016-03-01

    Biotechnology is the manufacturing technology of the future. However, engineering biology is complex, and many possible genetic designs must be evaluated to find cells that produce high levels of a desired drug or chemical. Recent advances have enabled the design and construction of billions of genetic variants per day, but evaluation capacity remains limited to thousands of variants per day. Here we evaluate biological engineering through the lens of the design–build–test cycle framework and highlight the role that multiplexing has had in transforming the design and build steps. We describe a multiplexed solution to the ‘test’ step that is enabled by new research. Achieving a multiplexed test step will permit a fully multiplexed engineering cycle and boost the throughput of biobased product development by up to a millionfold.

  17. DIC-CAM recipe for reverse engineering

    Science.gov (United States)

    Romero-Carrillo, P.; Lopez-Alba, E.; Dorado, R.; Diaz-Garrido, F. A.

    2012-04-01

    Reverse engineering (RE) tries to model and manufacture an object from measurements one of a reference object. Modern optical measurement systems and computer aided engineering software have improved reverse engineering procedures. We detail the main RE steps from 3D digitalization by Digital Image Correlation to manufacturing. The previous description is complemented with an application example, which portrays the performance of RE. The differences between original and manufactured objects are less than 2 mm (close to the tool radius).

  18. Reverse engineering of the robot base platform

    International Nuclear Information System (INIS)

    Anwar A Rahman; Azizul Rahman A Aziz; Mohd Arif Hamzah; Muhd Nor Atan; Fadil Ismail; Rosli Darmawan

    2009-01-01

    The robot base platform used to place the robotic arm version 2 was imported through a local company. The robot base platform is used as a reference for reverse egineering development for a smaller size robot. The paper will discuss the reverse engineering design process and parameters involved in the development of the robot base platform. (Author)

  19. Research regarding reverse engineering for aircraft components

    Directory of Open Access Journals (Sweden)

    Udroiu Razvan

    2017-01-01

    Full Text Available Reverse engineering is a useful technique used in manufacturing and design process of new components. In aerospace industry new components can be developed, based on existing components without technical Computer Aided Design (CAD data, in order to reduce the development cycle of new products. This paper proposes a methodology wherein the CAD model of turbine blade can be build using computer aided reverse engineering technique utilising a 5 axis Coordinate Measuring Machine (CMM. The proposed methodology uses a scanning strategy by features, followed by a design methodology for 3D modelling of complex shapes.

  20. A gene network simulator to assess reverse engineering algorithms.

    Science.gov (United States)

    Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

    2009-03-01

    In the context of reverse engineering of biological networks, simulators are helpful to test and compare the accuracy of different reverse-engineering approaches in a variety of experimental conditions. A novel gene-network simulator is presented that resembles some of the main features of transcriptional regulatory networks related to topology, interaction among regulators of transcription, and expression dynamics. The simulator generates network topology according to the current knowledge of biological network organization, including scale-free distribution of the connectivity and clustering coefficient independent of the number of nodes in the network. It uses fuzzy logic to represent interactions among the regulators of each gene, integrated with differential equations to generate continuous data, comparable to real data for variety and dynamic complexity. Finally, the simulator accounts for saturation in the response to regulation and transcription activation thresholds and shows robustness to perturbations. It therefore provides a reliable and versatile test bed for reverse engineering algorithms applied to microarray data. Since the simulator describes regulatory interactions and expression dynamics as two distinct, although interconnected aspects of regulation, it can also be used to test reverse engineering approaches that use both microarray and protein-protein interaction data in the process of learning. A first software release is available at http://www.dei.unipd.it/~dicamill/software/netsim as an R programming language package.

  1. Detecting A Botnet By Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Oesman Hendra Kelana

    2013-06-01

    Full Text Available Abstract— Botnet malware is a malicious program. Botnet that infects computers, called bots, will be controlled by a botmaster to do various things such as: spamming, phishing, keylogging Distributed Denial of Service (DDoS and other activities that are generally profitable to the owner of the bot (botmaster or those who use botnet services. The problem is that many computers have been controlled by botnets without the knowledge of the computer owner.  There are many ways to examine botnets, for example by studying the traffic from the botnet network, studying how botnets communicate to each, studying how each robot receives orders to do something, and so forth. Of the many methods, the most frequently and commonly used is the reverse engineering, where researchers study how a botnet works by botnet debugging. In this study the author tries to understand or research botnets by taking a type of botnet, namely Agobot, using reverse engineering.  One of the result of the research is that malware program files in general and in particular botnet has a technique to obscure the way that research using reverse engineering. Another result also shows that the botnet Agobot runs on computers by using the Windows service, and by changing the Windows registry so that every time the computer starts, Agobot always actively works in the computer memory. Keywords— Malware, Bot, Botnet, Botmaster, Agobot, Spam, Distributed Denial of Services, Identity Theft, Computer Security, Reverse Engineering, Debug, Windows Service, the Registry.

  2. Reversibility: An Engineer's Point of View

    Energy Technology Data Exchange (ETDEWEB)

    Berest, Pierre [LMS, ecole Polytechnique (France)

    2012-07-01

    Reversibility is the most consistent option in a democratic country. However reversibility may also have several drawbacks which must be identified and mitigated. Reversibility of a geological repository is a relatively new idea in France. The 1991 law dedicated to nuclear waste management considered reversibility as a possible option. Fifteen years later, the 2006 law mandated that a deep repository must be reversible and that the exact content of this notion should be defined by a new law to be discussed by the Parliament in 2015. Reversibility was not a concern put forward by engineers. It clearly originated from a societal demand sponsored and formulated by the Parliament. Since 1991, the exact meaning of this mandate progressively became more precise. In the early days, reversibility meant the technical and financial capability to retrieve the wastes from the repository, at least for some period of time after being emplaced. Progressively, a broader definition, suggested by Andra, was accepted: reversibility also means that a disposal facility should be operated in such a way that a stepwise decision-making process is possible. At each step, society must be able to decide to proceed to the next step, to pause or to reverse a step. Several benefits can be expected from a reversible repository. Some technical safety concerns may be only recognised after waste emplacement. Radioactive wastes may become a resource whose recoverability is desirable. Regulations may change, alternative waste treatment or better disposal techniques may be developed, or the need to modify a component of the facility may arise. Looking back at how chemical or domestic wastes were managed some 50 years ago easily underscores that it is not unreasonable to hope for significant advances in the future. For scientists and engineers, reversibility proves to have several other merits. To design and build a good repository, time is needed. The operator of a mine or of an oil field knows that

  3. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  4. A Predictive Approach to Network Reverse-Engineering

    Science.gov (United States)

    Wiggins, Chris

    2005-03-01

    A central challenge of systems biology is the ``reverse engineering" of transcriptional networks: inferring which genes exert regulatory control over which other genes. Attempting such inference at the genomic scale has only recently become feasible, via data-intensive biological innovations such as DNA microrrays (``DNA chips") and the sequencing of whole genomes. In this talk we present a predictive approach to network reverse-engineering, in which we integrate DNA chip data and sequence data to build a model of the transcriptional network of the yeast S. cerevisiae capable of predicting the response of genes in unseen experiments. The technique can also be used to extract ``motifs,'' sequence elements which act as binding sites for regulatory proteins. We validate by a number of approaches and present comparison of theoretical prediction vs. experimental data, along with biological interpretations of the resulting model. En route, we will illustrate some basic notions in statistical learning theory (fitting vs. over-fitting; cross- validation; assessing statistical significance), highlighting ways in which physicists can make a unique contribution in data- driven approaches to reverse engineering.

  5. Variable Cycle Intake for Reverse Core Engine

    Science.gov (United States)

    Suciu, Gabriel L (Inventor); Chandler, Jesse M (Inventor); Staubach, Joseph B (Inventor)

    2016-01-01

    A gas generator for a reverse core engine propulsion system has a variable cycle intake for the gas generator, which variable cycle intake includes a duct system. The duct system is configured for being selectively disposed in a first position and a second position, wherein free stream air is fed to the gas generator when in the first position, and fan stream air is fed to the gas generator when in the second position.

  6. Efficient Reverse-Engineering of a Developmental Gene Regulatory Network

    Science.gov (United States)

    Cicin-Sain, Damjan; Ashyraliyev, Maksat; Jaeger, Johannes

    2012-01-01

    Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a major problem in biology. Computational models can be used as tools to extract the regulatory structure and dynamics of such networks from gene expression data. This approach is called reverse engineering. It has been successfully applied to many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmental gene network in its spatial context remains a considerable challenge. Here, we address this challenge using a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipeline that considerably increases the throughput of the method, but results in data of reduced accuracy compared to those previously used for gap gene network inference. We demonstrate that we can infer the correct network structure using our reduced data set, and investigate minimal data requirements for successful reverse engineering. Our results show that timing and position of expression domain boundaries are the crucial features for determining regulatory network structure from data, while it is less important to precisely measure expression levels. Based on this, we define minimal data requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in different developmental contexts and organisms. Such systematic application of data-driven models to real-world networks has enormous potential. Only the quantitative investigation of a large number of developmental gene regulatory networks will allow us to

  7. Understanding Virtual Objects through Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Vera Moitinho

    2012-11-01

    Full Text Available The main objective of our research is to develop a new methodology, based on Reverse Engineering processes – 3D scan, quantitative data analysis and Artificial Intelligence techniques, in particular simulation – to study the relationship between form and function of artefacts. Furthermore, we aim to provide new data, as well as possible explanations of the archaeological record according to what it expects about social activity, including working processes, by simulating the potentialities of such actions in terms of input-output relationships.

  8. High Pressure Reverse Flow APS Engine

    Science.gov (United States)

    Senneff, J. M.

    1972-01-01

    A design and test demonstration effort was undertaken to evaluate the concept of the reverse flow engine for the APS engine application. The 1500 lb (6672 N) thrust engine was designed to operate on gaseous hydrogen and gaseous oxygen propellants at a mixture ratio of 4 and to achieve the objective performance of 435 sec (4266 Nsec/kg) specific impulse. Superimposed durability requirements called for a million-cycle capability with 50 hours duration. The program was undertaken as a series of tasks including the initial preliminary design, design of critical test components and finally, the design and demonstration of an altitude engine which could be used interchangeably to examine operating parameters as well as to demonstrate the capability of the concept. The program results are reported with data to indicate that all of the program objectives were met or exceeded within the course of testing on the program. The analysis effort undertaken is also reported in detail and supplemented with test data in some cases where prior definitions could not be made. The results are contained of these analyses as well as the test results conducted throughout the course of the program. Finally, the test data and analytical results were combined to allow recommendations for a flight weight design. This preliminary design effort is also detailed.

  9. Synthetic biology: engineering molecular computers

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    Complicated systems cannot survive the rigors of a chaotic environment, without balancing mechanisms that sense, decide upon and counteract the exerted disturbances. Especially so with living organisms, forced by competition to incredible complexities, escalating also their self-controlling plight. Therefore, they compute. Can we harness biological mechanisms to create artificial computing systems? Biology offers several levels of design abstraction: molecular machines, cells, organisms... ranging from the more easily-defined to the more inherently complex. At the bottom of this stack we find the nucleic acids, RNA and DNA, with their digital structure and relatively precise interactions. They are central enablers of designing artificial biological systems, in the confluence of engineering and biology, that we call Synthetic biology. In the first part, let us follow their trail towards an overview of building computing machines with molecules -- and in the second part, take the case study of iGEM Greece 201...

  10. Mammalian Synthetic Biology: Engineering Biological Systems.

    Science.gov (United States)

    Black, Joshua B; Perez-Pinera, Pablo; Gersbach, Charles A

    2017-06-21

    The programming of new functions into mammalian cells has tremendous application in research and medicine. Continued improvements in the capacity to sequence and synthesize DNA have rapidly increased our understanding of mechanisms of gene function and regulation on a genome-wide scale and have expanded the set of genetic components available for programming cell biology. The invention of new research tools, including targetable DNA-binding systems such as CRISPR/Cas9 and sensor-actuator devices that can recognize and respond to diverse chemical, mechanical, and optical inputs, has enabled precise control of complex cellular behaviors at unprecedented spatial and temporal resolution. These tools have been critical for the expansion of synthetic biology techniques from prokaryotic and lower eukaryotic hosts to mammalian systems. Recent progress in the development of genome and epigenome editing tools and in the engineering of designer cells with programmable genetic circuits is expanding approaches to prevent, diagnose, and treat disease and to establish personalized theranostic strategies for next-generation medicines. This review summarizes the development of these enabling technologies and their application to transforming mammalian synthetic biology into a distinct field in research and medicine.

  11. Synthetic biology meets tissue engineering.

    Science.gov (United States)

    Davies, Jamie A; Cachat, Elise

    2016-06-15

    Classical tissue engineering is aimed mainly at producing anatomically and physiologically realistic replacements for normal human tissues. It is done either by encouraging cellular colonization of manufactured matrices or cellular recolonization of decellularized natural extracellular matrices from donor organs, or by allowing cells to self-organize into organs as they do during fetal life. For repair of normal bodies, this will be adequate but there are reasons for making unusual, non-evolved tissues (repair of unusual bodies, interface to electromechanical prostheses, incorporating living cells into life-support machines). Synthetic biology is aimed mainly at engineering cells so that they can perform custom functions: applying synthetic biological approaches to tissue engineering may be one way of engineering custom structures. In this article, we outline the 'embryological cycle' of patterning, differentiation and morphogenesis and review progress that has been made in constructing synthetic biological systems to reproduce these processes in new ways. The state-of-the-art remains a long way from making truly synthetic tissues, but there are now at least foundations for future work. © 2016 Authors; published by Portland Press Limited.

  12. Reverse engineering of inductive fault current limiters

    Energy Technology Data Exchange (ETDEWEB)

    Pina, J M; Neves, M Ventim; Rodrigues, A L [Centre of Technology and Systems Faculdade de Ciencias e Tecnologia, Nova University of Lisbon Monte de Caparica, 2829-516 Caparica (Portugal); Suarez, P; Alvarez, A, E-mail: jmmp@fct.unl.p [' Benito Mahedero' Group of Electrical Applications of Superconductors Escuela de IngenierIas Industrials, University of Extremadura Avenida de Elvas s/n, 06006 Badajoz (Spain)

    2010-06-01

    The inductive fault current limiter is less compact and harder to scale to high voltage networks than the resistive one. Nevertheless, its simple construction and mechanical robustness make it attractive in low voltage grids. Thus, it might be an enabling technology for the advent of microgrids, low voltage networks with dispersed generation, controllable loads and energy storage. A new methodology for reverse engineering of inductive fault current limiters based on the independent analysis of iron cores and HTS cylinders is presented in this paper. Their electromagnetic characteristics are used to predict the devices' hysteresis loops and consequently their dynamic behavior. Previous models based on the separate analysis of the limiters' components were already derived, e.g. in transformer like equivalent models. Nevertheless, the assumptions usually made may limit these models' application, as shown in the paper. The proposed methodology obviates these limitations. Results are validated through simulations.

  13. Reverse engineering of inductive fault current limiters

    International Nuclear Information System (INIS)

    Pina, J M; Neves, M Ventim; Rodrigues, A L; Suarez, P; Alvarez, A

    2010-01-01

    The inductive fault current limiter is less compact and harder to scale to high voltage networks than the resistive one. Nevertheless, its simple construction and mechanical robustness make it attractive in low voltage grids. Thus, it might be an enabling technology for the advent of microgrids, low voltage networks with dispersed generation, controllable loads and energy storage. A new methodology for reverse engineering of inductive fault current limiters based on the independent analysis of iron cores and HTS cylinders is presented in this paper. Their electromagnetic characteristics are used to predict the devices' hysteresis loops and consequently their dynamic behavior. Previous models based on the separate analysis of the limiters' components were already derived, e.g. in transformer like equivalent models. Nevertheless, the assumptions usually made may limit these models' application, as shown in the paper. The proposed methodology obviates these limitations. Results are validated through simulations.

  14. Application of industrial CT in reverse engineering technology

    International Nuclear Information System (INIS)

    Fang Liyong; Li Hui; Bai Jinping; Li Bailin

    2013-01-01

    The basic principle and basic steps of reverse engineering technology based on industrial CT are described. The recent research progresses and situation at home and abroad of reverse engineering technology based on industrial CT image are respectively described, analyzed and summarized from two routes which are surface segmentation and volume segmentation. An example of conch is used to exhibit the results from the two routes in reverse engineering technology based on industrial CT image. Finally, some difficulties in application and the future developments of reverse engineering technology based on industrial CT are prospected. (authors)

  15. Synthetic biology: an emerging engineering discipline.

    Science.gov (United States)

    Cheng, Allen A; Lu, Timothy K

    2012-01-01

    Over the past decade, synthetic biology has emerged as an engineering discipline for biological systems. Compared with other substrates, biology poses a unique set of engineering challenges resulting from an incomplete understanding of natural biological systems and tools for manipulating them. To address these challenges, synthetic biology is advancing from developing proof-of-concept designs to focusing on core platforms for rational and high-throughput biological engineering. These platforms span the entire biological design cycle, including DNA construction, parts libraries, computational design tools, and interfaces for manipulating and probing synthetic circuits. The development of these enabling technologies requires an engineering mindset to be applied to biology, with an emphasis on generalizable techniques in addition to application-specific designs. This review aims to discuss the progress and challenges in synthetic biology and to illustrate areas where synthetic biology may impact biomedical engineering and human health.

  16. A Biological Porin Engineered into a Molecular, Nanofluidic Diode

    NARCIS (Netherlands)

    Miedema, Henk; Vrouenraets, Maarten; Wierenga, Jenny; Meijberg, Wim; Robillard, George; Eisenberg, Bob

    2007-01-01

    We changed the nonrectifying biological porin OmpF into a nanofluidic diode. To that end, we engineered a pore that possesses two spatially separated selectivity filters of opposite charge where either cations or anions accumulate. The observed current inhibition under applied reverse bias voltage

  17. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Galitski, Timothy P.

    2008-04-01

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

  18. Biology: An Important Agricultural Engineering Mechanism

    Science.gov (United States)

    Henderson, S. M.

    1974-01-01

    Describes the field of bioengineering with particular emphasis on agricultural engineering, and presents the results of a survey of schools that combine biology and engineering in their curricula. (JR)

  19. Novel combination of reverse engineering and vapid prototyping in medicine

    CSIR Research Space (South Africa)

    Schenker, R

    1999-08-01

    Full Text Available The technologies of reverse engineering and rapid prototyping are emerging as useful new tools in medicine. One application is of particular interest in orthopaedic, dental and reconstructive surgery. It involves the imaging, modelling...

  20. Reverse Engineering Integrated Circuits Using Finite State Machine Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Oler, Kiri J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Miller, Carl H. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-04-12

    In this paper, we present a methodology for reverse engineering integrated circuits, including a mathematical verification of a scalable algorithm used to generate minimal finite state machine representations of integrated circuits.

  1. Vertical Integration and Reverse Engineering of Agricultural Enterprises

    Institute of Scientific and Technical Information of China (English)

    Gang; WU; Yong; DU

    2014-01-01

    This paper studies the potential effects of agricultural enterprise’s vertical integration and reverse engineering on downstream firms.Suppliers who invest reverse engineering technology can exploit customer’s information. An integrated supplier can obtain at no cost the information from its subsidiary. Based on repeated game and considered corporate " good" or " bad" type,this paper analysis supplier’s selection and downstream investment in innovation. The results showed that: when the cost is higher than the threshold value no company invest in reverse engineering,when the cost is lower than the threshold value the integration company invest in reverse engineering; in the second period,vertical integration reduce the downstream independent enterprise’s innovation investment and profits,integrated enterprise increase innovation investment and profits; during the first period of the game,the independent downstream firms being " completely foreclosure".

  2. Reverse Engineering Camouflaged Sequential Integrated Circuits Without Scan Access

    OpenAIRE

    Massad, Mohamed El; Garg, Siddharth; Tripunitara, Mahesh

    2017-01-01

    Integrated circuit (IC) camouflaging is a promising technique to protect the design of a chip from reverse engineering. However, recent work has shown that even camouflaged ICs can be reverse engineered from the observed input/output behaviour of a chip using SAT solvers. However, these so-called SAT attacks have so far targeted only camouflaged combinational circuits. For camouflaged sequential circuits, the SAT attack requires that the internal state of the circuit is controllable and obser...

  3. Integrating rehabilitation engineering technology with biologics.

    Science.gov (United States)

    Collinger, Jennifer L; Dicianno, Brad E; Weber, Douglas J; Cui, Xinyan Tracy; Wang, Wei; Brienza, David M; Boninger, Michael L

    2011-06-01

    Rehabilitation engineers apply engineering principles to improve function or to solve challenges faced by persons with disabilities. It is critical to integrate the knowledge of biologics into the process of rehabilitation engineering to advance the field and maximize potential benefits to patients. Some applications in particular demonstrate the value of a symbiotic relationship between biologics and rehabilitation engineering. In this review we illustrate how researchers working with neural interfaces and integrated prosthetics, assistive technology, and biologics data collection are currently integrating these 2 fields. We also discuss the potential for further integration of biologics and rehabilitation engineering to deliver the best technologies and treatments to patients. Engineers and clinicians must work together to develop technologies that meet clinical needs and are accessible to the intended patient population. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  4. Android Application Protection against Static Reverse Engineering based on Multidexing

    Directory of Open Access Journals (Sweden)

    Nak Young Kim

    2016-11-01

    Full Text Available DEX files are executable files of Android applications. Since DEX files are in the format of Java bytecodes, their Java source codes can be easily obtained using static reverse engineering tools. This results in numerous Android application thefts. There are some tools (e.g. bangcle, ijiami, liapp that protect Android applications against static reverse engineering utilizing dynamic code loading. These tools usually encrypt classes.dex in an APK file. When the application is launched, the encrypted classes.dex file is decrypted and dynamically loaded. However, these tools fail to protect multidex APKs, which include more than one DEX files (classes2.dex, classes3.dex, ... to accommodate large-sized execution codes. In this paper, we propose a technique that protects multidex Android applications against static reverse engineering. The technique can encrypt/decrypt multiple DEX files in APK files and dynamically load them. The experimental results show that the proposed technique can effiectively protect multidex APKs.

  5. Parametric Optimization Design of Brake Block Based on Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Jin Hua-wei

    2017-01-01

    Full Text Available As one of the key part of automotive brake,the performance of brake block has a direct impact on the safety and comfort of cars. Modeling the brake block of disc brake in reverse parameterization by reverse engineering software, analyzing and optimizing the reconstructed model by CAE software. Processing the scanned point cloud by Geomagic Studio and reconstructing the CAD model of the brake block with the parametric surface function of the software, then analyzing and optimizing it by Wrokbench. The example shows that it is quick to reconstruct the CAD model of parts by using reverse parameterization method and reduce part re-design development cycle significantly.

  6. Application of reverse engineering in the medical industry.

    Science.gov (United States)

    Kaleev, A. A.; Kashapov, L. N.; Kashapov, N. F.; Kashapov, R. N.

    2017-09-01

    The purpose of this research is to develop on the basis of existing analogs new design of ophthalmologic microsurgical tweezers by using reverse engineering techniques. Virtual model was obtained by using a three-dimensional scanning system Solutionix Rexcan 450 MP. Geomagic Studio program was used to remove defects and inaccuracies of the obtained parametric model. A prototype of the finished model was made on the installation of laser stereolithography Projet 6000. Total time of the creation was 16 hours from the reverse engineering procedure to 3D-printing of the prototype.

  7. Synthetic Biology to Engineer Bacteriophage Genomes.

    Science.gov (United States)

    Rita Costa, Ana; Milho, Catarina; Azeredo, Joana; Pires, Diana Priscila

    2018-01-01

    Recent advances in the synthetic biology field have enabled the development of new molecular biology techniques used to build specialized bacteriophages with new functionalities. Bacteriophages have been engineered towards a wide range of applications including pathogen control and detection, targeted drug delivery, or even assembly of new materials.In this chapter, two strategies that have been successfully used to genetically engineer bacteriophage genomes are addressed: a yeast-based platform and bacteriophage recombineering of electroporated DNA.

  8. Teach CAD and Measuring Skills through Reverse Engineering

    Science.gov (United States)

    Board, Keith

    2012-01-01

    This article describes a reverse engineering activity that gives students hands-on, minds-on experience with measuring tools, machine parts, and CAD. The author developed this activity to give students an abundance of practical experience with measuring tools. Equally important, it provides a good interface between the virtual world of CAD 3D…

  9. Synthetic biology approaches to engineer T cells.

    Science.gov (United States)

    Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T; Lim, Wendell A

    2015-08-01

    There is rapidly growing interest in learning how to engineer immune cells, such as T lymphocytes, because of the potential of these engineered cells to be used for therapeutic applications such as the recognition and killing of cancer cells. At the same time, our knowhow and capability to logically engineer cellular behavior is growing rapidly with the development of synthetic biology. Here we describe how synthetic biology approaches are being used to rationally alter the behavior of T cells to optimize them for therapeutic functions. We also describe future developments that will be important in order to construct safe and precise T cell therapeutics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Biologi og/eller engineering?

    DEFF Research Database (Denmark)

    Daugbjerg, Peer

    2018-01-01

    Engineering i skolen er en anvendelsesorienteret og problemløsende undervisning, hvor eleverne lærer at udvikle konkrete løsninger på praktiske problemer. I elevernes arbejde indgår faglig viden og teknologi...

  11. An engineering design approach to systems biology.

    Science.gov (United States)

    Janes, Kevin A; Chandran, Preethi L; Ford, Roseanne M; Lazzara, Matthew J; Papin, Jason A; Peirce, Shayn M; Saucerman, Jeffrey J; Lauffenburger, Douglas A

    2017-07-17

    Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact. Here, we articulate an engineering approach to systems biology, which applies educational philosophy, engineering design, and predictive models to solve contemporary problems in an age of biomedical Big Data. A concerted effort to train systems bioengineers will provide a versatile workforce capable of tackling the diverse challenges faced by the biotechnological and pharmaceutical sectors in a modern, information-dense economy.

  12. Biological Systems Thinking for Control Engineering Design

    Directory of Open Access Journals (Sweden)

    D. J. Murray-Smith

    2004-01-01

    Full Text Available Artificial neural networks and genetic algorithms are often quoted in discussions about the contribution of biological systems thinking to engineering design. This paper reviews work on the neuromuscular system, a field in which biological systems thinking could make specific contributions to the development and design of automatic control systems for mechatronics and robotics applications. The paper suggests some specific areas in which a better understanding of this biological control system could be expected to contribute to control engineering design methods in the future. Particular emphasis is given to the nonlinear nature of elements within the neuromuscular system and to processes of neural signal processing, sensing and system adaptivity. Aspects of the biological system that are of particular significance for engineering control systems include sensor fusion, sensor redundancy and parallelism, together with advanced forms of signal processing for adaptive and learning control. 

  13. Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.

    Science.gov (United States)

    Willing, Ryan; King, Graham J W; Johnson, James A

    2015-11-26

    Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (pengineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom-Programmable Circuits

    Science.gov (United States)

    2017-03-23

    Introduction The widely practiced horizontal integrated circuit supply chain exposes a design to various types of attacks including the reverse engineering ...STT_CMOS designs for reverse- engineering prevention, DAC 2016. [5] M. E. Massad and et. al. Integrated circuit (IC) decamouflaging: reverse...The ATPG Attack for Reverse Engineering of Combinational Hybrid Custom-Programmable Circuits Raza Shafiq Hamid Mahmoodi Houman Homayoun Hassan

  15. Benefits of reverse engineering technologies in software development makerspace

    Directory of Open Access Journals (Sweden)

    Aabidi M.H.

    2017-01-01

    Full Text Available In the recent decades, the amount of data produced by scientific, engineering, and life science applications has increased with several orders of magnitude. In parallel with this development, the applications themselves have become increasingly complex in terms of functionality, structure, and behavior. In the same time, development and production cycles of such applications exhibit a tendency of becoming increasingly shorter, due to factors such as market pressure and rapid evolution of supporting and enabling technologies. As a consequence, an increasing fraction of the cost of creating new applications and manufacturing processes shifts from the creation of new artifacts to the adaption of existing ones. A key component of this activity is the understanding of the design, operation, and behavior of existing manufactured artifacts, such as software code bases, hardware systems, and mechanical assemblies. For instance, in the software industry, it is estimated that maintenance costs exceed 80% of the total costs of a software product's lifecycle, and software understanding accounts for as much as half of these maintenance costs. To facilitate the software development process, it would be ideal to have tools that automatically generate or help to generate UML (Unified Modeling Language models from source code. Reverse engineering the software architecture from source code provides a valuable service to software practitioners. Case tools implementing MDA and reverse-engineering constitute an important opportunity of software development engineers. So MDA and reverse engineering is an important key witch make makerspace more productive and more efficient.

  16. Reversible and irreversible heat engine and refrigerator cycles

    Science.gov (United States)

    Leff, Harvey S.

    2018-05-01

    Although no reversible thermodynamic cycles exist in nature, nearly all cycles covered in textbooks are reversible. This is a review, clarification, and extension of results and concepts for quasistatic, reversible and irreversible processes and cycles, intended primarily for teachers and students. Distinctions between the latter process types are explained, with emphasis on clockwise (CW) and counterclockwise (CCW) cycles. Specific examples of each are examined, including Carnot, Kelvin and Stirling cycles. For the Stirling cycle, potentially useful task-specific efficiency measures are proposed and illustrated. Whether a cycle behaves as a traditional refrigerator or heat engine can depend on whether it is reversible or irreversible. Reversible and irreversible-quasistatic CW cycles both satisfy Carnot's inequality for thermal efficiency, η ≤ η C a r n o t . Irreversible CCW cycles with two reservoirs satisfy the coefficient of performance inequality K ≤ K C a r n o t . However, an arbitrary reversible cycle satisfies K ≥ K C a r n o t when compared with a reversible Carnot cycle operating between its maximum and minimum temperatures, a potentially counterintuitive result.

  17. Biological aspects of tissue-engineered cartilage.

    Science.gov (United States)

    Hoshi, Kazuto; Fujihara, Yuko; Yamawaki, Takanori; Harai, Motohiro; Asawa, Yukiyo; Hikita, Atsuhiko

    2018-04-01

    Cartilage regenerative medicine has been progressed well, and it reaches the stage of clinical application. Among various techniques, tissue engineering, which incorporates elements of materials science, is investigated earnestly, driven by high clinical needs. The cartilage tissue engineering using a poly lactide scaffold has been exploratorily used in the treatment of cleft lip-nose patients, disclosing good clinical results during 3-year observation. However, to increase the reliability of this treatment, not only accumulation of clinical evidence on safety and usefulness of the tissue-engineered products, but also establishment of scientific background on biological mechanisms, are regarded essential. In this paper, we reviewed recent trends of cartilage tissue engineering in clinical practice, summarized experimental findings on cellular and matrix changes during the cartilage regeneration, and discussed the importance of further studies on biological aspects of tissue-engineered cartilage, especially by the histological and the morphological methods.

  18. Reverse engineering validation using a benchmark synthetic gene circuit in human cells.

    Science.gov (United States)

    Kang, Taek; White, Jacob T; Xie, Zhen; Benenson, Yaakov; Sontag, Eduardo; Bleris, Leonidas

    2013-05-17

    Multicomponent biological networks are often understood incompletely, in large part due to the lack of reliable and robust methodologies for network reverse engineering and characterization. As a consequence, developing automated and rigorously validated methodologies for unraveling the complexity of biomolecular networks in human cells remains a central challenge to life scientists and engineers. Today, when it comes to experimental and analytical requirements, there exists a great deal of diversity in reverse engineering methods, which renders the independent validation and comparison of their predictive capabilities difficult. In this work we introduce an experimental platform customized for the development and verification of reverse engineering and pathway characterization algorithms in mammalian cells. Specifically, we stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies. The network, which is orthogonal to endogenous cellular signaling, contains a small set of regulatory interactions that can be used to quantify the reconstruction performance. By performing successive perturbations to each modular component of the network and comparing protein and RNA measurements, we study the conditions under which we can reliably reconstruct the causal relationships of the integrated synthetic network.

  19. Mobile Timekeeping Application Built on Reverse-Engineered JPL Infrastructure

    Science.gov (United States)

    Witoff, Robert J.

    2013-01-01

    Every year, non-exempt employees cumulatively waste over one man-year tracking their time and using the timekeeping Web page to save those times. This app eliminates this waste. The innovation is a native iPhone app. Libraries were built around a reverse- engineered JPL API. It represents a punch-in/punch-out paradigm for timekeeping. It is accessible natively via iPhones, and features ease of access. Any non-exempt employee can natively punch in and out, as well as save and view their JPL timecard. This app is built on custom libraries created by reverse-engineering the standard timekeeping application. Communication is through custom libraries that re-route traffic through BrowserRAS (remote access service). This has value at any center where employees track their time.

  20. Computer-aided dental prostheses construction using reverse engineering.

    Science.gov (United States)

    Solaberrieta, E; Minguez, R; Barrenetxea, L; Sierra, E; Etxaniz, O

    2014-01-01

    The implementation of computer-aided design/computer-aided manufacturing (CAD/CAM) systems with virtual articulators, which take into account the kinematics, constitutes a breakthrough in the construction of customised dental prostheses. This paper presents a multidisciplinary protocol involving CAM techniques to produce dental prostheses. This protocol includes a step-by-step procedure using innovative reverse engineering technologies to transform completely virtual design processes into customised prostheses. A special emphasis is placed on a novel method that permits a virtual location of the models. The complete workflow includes the optical scanning of the patient, the use of reverse engineering software and, if necessary, the use of rapid prototyping to produce CAD temporary prostheses.

  1. Tissue-Engineered Skeletal Muscle Organoids for Reversible Gene Therapy

    Science.gov (United States)

    Vandenburgh, Herman; DelTatto, Michael; Shansky, Janet; Lemaire, Julie; Chang, Albert; Payumo, Francis; Lee, Peter; Goodyear, Amy; Raven, Latasha

    1996-01-01

    Genetically modified murine skeletal myoblasts were tissue engineered in vitro into organ-like structures (organoids) containing only postmitotic myofibers secreting pharmacological levels of recombinant human growth hormone (rhGH). Subcutaneous organoid Implantation under tension led to the rapid and stable appearance of physiological sera levels of rhGH for up to 12 weeks, whereas surgical removal led to its rapid disappearance. Reversible delivery of bioactive compounds from postimtotic cells in tissue engineered organs has several advantages over other forms of muscle gene therapy.

  2. Cranioplasty prosthesis manufacturing based on reverse engineering technology

    Science.gov (United States)

    Chrzan, Robert; Urbanik, Andrzej; Karbowski, Krzysztof; Moskała, Marek; Polak, Jarosław; Pyrich, Marek

    2012-01-01

    Summary Background Most patients with large focal skull bone loss after craniectomy are referred for cranioplasty. Reverse engineering is a technology which creates a computer-aided design (CAD) model of a real structure. Rapid prototyping is a technology which produces physical objects from virtual CAD models. The aim of this study was to assess the clinical usefulness of these technologies in cranioplasty prosthesis manufacturing. Material/Methods CT was performed on 19 patients with focal skull bone loss after craniectomy, using a dedicated protocol. A material model of skull deficit was produced using computer numerical control (CNC) milling, and individually pre-operatively adjusted polypropylene-polyester prosthesis was prepared. In a control group of 20 patients a prosthesis was manually adjusted to each patient by a neurosurgeon during surgery, without using CT-based reverse engineering/rapid prototyping. In each case, the prosthesis was implanted into the patient. The mean operating times in both groups were compared. Results In the group of patients with reverse engineering/rapid prototyping-based cranioplasty, the mean operating time was shorter (120.3 min) compared to that in the control group (136.5 min). The neurosurgeons found the new technology particularly useful in more complicated bone deficits with different curvatures in various planes. Conclusions Reverse engineering and rapid prototyping may reduce the time needed for cranioplasty neurosurgery and improve the prosthesis fitting. Such technologies may utilize data obtained by commonly used spiral CT scanners. The manufacturing of individually adjusted prostheses should be commonly used in patients planned for cranioplasty with synthetic material. PMID:22207125

  3. Biometrics in wearable products: Reverse Engineering and numerical modeling

    OpenAIRE

    Rao, Andrea

    2011-01-01

    The Reverse Engineering (RE) techniques and the Finite Element Modelling (FEM) are widely used tools in many scientific fields. They were firstly developed for the mechanics but in the last times became common for other disciplines. In the thesis these techniques are used for the customization of the wearable products. It is possible to observe that the geometry of whatever wearable product is fundamental for the comfort. In particular, starting from the need of wearable product it is possibl...

  4. Reverse electrodialysis heat engine for sustainable power production

    International Nuclear Information System (INIS)

    Tamburini, A.; Tedesco, M.; Cipollina, A.; Micale, G.; Ciofalo, M.; Papapetrou, M.; Van Baak, W.; Piacentino, A.

    2017-01-01

    Graphical abstract: State of the art technologies for the conversion of heat into power. Grey circles refer to technologies at very early stage of development and non-available at industrial level. The Carnot efficiency (on the secondary horizontal axis) is evaluated assuming a cold sink temperature of 25 °C. SRC-hot gases: Steam Rankine Cycle integrated with gas turbine/other topping cycles; SRC-fuel: Steam Rankine Cycle directly fuelled by oil, coal or other fuels; KC: Kalina Cycle; ORC: Organic Rankine Cycle; TEG: Thermoelectric Generation; PEPG: Piezoelectric Power Generation with waste heat-powered expansion/compression cycle; OHE: Osmotic Heat Engine; REDHE, Reverse Electrodialysis Heat Engine (this paper). Display Omitted -- Highlights: •For the first time, the potential of Reverse Electrodialysis Heat Engine is assessed. •An overview of the possible regeneration methods is presented. •Performance of the RED unit fed by different salty solutions was suitably optimized. •Three different RED Heat Engine scenarios were studied. •Exergetic efficiency of about 85% could be achieved in the foreseen future. -- Abstract: Reverse Electrodialysis Heat Engine (REDHE) is a promising technology to convert waste heat at temperatures lower than 100 °C into electric power. In the present work an overview of the possible regeneration methods is presented and the technological challenges for the development of the RED Heat Engine (REDHE) are identified. The potential of this power production cycle was investigated through a simplified mathematical model. In the first part of the work, several salts were singularly modelled as possible solutes in aqueous solutions feeding the RED unit and the corresponding optimal conditions were recognized via an optimization study. In the second part, three different RED Heat Engine scenarios were studied. Results show that power densities much higher than those relevant to NaCl-water solutions can be obtained by using different

  5. Strategies for replacement of obsolete equipment - including reverse engineering

    International Nuclear Information System (INIS)

    Irish, C.S.

    2000-01-01

    The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of: commercially available equivalent component; modification of a commercial available component; reverse engineering of the original component; and finally, design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: Missing, misleading or no information on the original component; Acquiring information from the original equipment manufacturer and the plant; Using a sample component for the replacement evaluation and or reverse engineering; and Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

  6. Critical evaluation of reverse engineering tool Imagix 4D!

    Science.gov (United States)

    Yadav, Rashmi; Patel, Ravindra; Kothari, Abhay

    2016-01-01

    The comprehension of legacy codes is difficult to understand. Various commercial reengineering tools are available that have unique working styles, and are equipped with their inherent capabilities and shortcomings. The focus of the available tools is in visualizing static behavior not the dynamic one. Therefore, it is difficult for people who work in software product maintenance, code understanding reengineering/reverse engineering. Consequently, the need for a comprehensive reengineering/reverse engineering tool arises. We found the usage of Imagix 4D to be good as it generates the maximum pictorial representations in the form of flow charts, flow graphs, class diagrams, metrics and, to a partial extent, dynamic visualizations. We evaluated Imagix 4D with the help of a case study involving a few samples of source code. The behavior of the tool was analyzed on multiple small codes and a large code gcc C parser. Large code evaluation was performed to uncover dead code, unstructured code, and the effect of not including required files at preprocessing level. The utility of Imagix 4D to prepare decision density and complexity metrics for a large code was found to be useful in getting to know how much reengineering is required. At the outset, Imagix 4D offered limitations in dynamic visualizations, flow chart separation (large code) and parsing loops. The outcome of evaluation will eventually help in upgrading Imagix 4D and posed a need of full featured tools in the area of software reengineering/reverse engineering. It will also help the research community, especially those who are interested in the realm of software reengineering tool building.

  7. Strategies for replacement of obsolete equipment, including reverse engineering

    International Nuclear Information System (INIS)

    Irish, C.S.

    2003-01-01

    The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of, (1) commercially available equivalent component, (2) modification of a commercial available component, (3) reverse engineering of the original component and finally (4) design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: 1) Missing, misleading or no information on the original component. 2) Acquiring information from the original equipment manufacturer and the plant. 3) Using a sample component for the replacement evaluation and or reverse engineering. 4) Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

  8. Graphical User Interfaces Reverse Engineering for Requirements Elicitation - Literature Review

    Directory of Open Access Journals (Sweden)

    Carol Jaimes

    2016-06-01

    Full Text Available This paper exhibits a synthesis of the use of legacy systems GUI reverse engineering as a tool to software requirements elicitation. It presents a literature review describing the approaches related to the topic. This work primary goal is to determine the major investigations in this area, and if there are techniques focused exclusively on the observation of the legacy applications GUI to obtain software requirements in a standard format, without the use of source code, data structures, documentation or sophisticated algorithms for the application analysis.

  9. Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

    Science.gov (United States)

    Lu, Kai; Gordon, Richard; Cao, Tong

    2015-03-01

    The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.

  10. Drag reduction of a reverse-engineered vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Lecrivain, G.; Slaouti, A.; Kennedy, I. [Manchester Metropolitan Univ., Manchester (United Kingdom). Dept. of Engineering and Technology

    2007-08-09

    The aerodynamic performance of a hand-made sports car was numerically assessed using computational fluid dynamics (CFD) analysis of various shape modifications. The purpose was to achieve a lower drag design. Reverse-engineering was used to create a virtual model of complex 3D shapes for which no computer-aided drawings (CAD) data existed. From the predicted flow, the body could be redesigned for better performance prior to its remanufacturing. This paper described the multidisciplinary procedure involving reverse-engineering and CAD that was used to recreate a suitable watertight model of the sports car. The different errors embedded in the successive stages leading to the final model were accurately assessed and minimized. The whole vehicle was remodelled for drag reduction. Surface reconstruction was carried out, an an accurate set of high quality Non-Uniform Rational B-Spline (NURBS) surfaces was produced over the polygonal mesh resulting in a fine visual surface finish with smooth lines and contours, as required in the automotive industry. Further modifications were implemented for the purpose of drag reduction and to improve its aerodynamic performance. The application described in this paper can be extended to any other similarly intricate vehicle or industrial component. 12 refs., 1 tab., 11 figs.

  11. Adding Robustness to Support Vector Machines Against Adversarial Reverse Engineering

    KAUST Repository

    Alabdulmohsin, Ibrahim

    2014-01-01

    Many classification algorithms have been successfully deployed in security-sensitive applications including spam filters and intrusion detection systems. Under such adversarial environments, adversaries can generate exploratory attacks against the defender such as evasion and reverse engineering. In this paper, we discuss why reverse engineering attacks can be carried out quite efficiently against fixed classifiers, and investigate the use of randomization as a suitable strategy for mitigating their risk. In particular, we derive a semidefinite programming (SDP) formulation for learning a distribution of classifiers subject to the constraint that any single classifier picked at random from such distribution provides reliable predictions with a high probability. We analyze the tradeoff between variance of the distribution and its predictive accuracy, and establish that one can almost always incorporate randomization with large variance without incurring a loss in accuracy. In other words, the conventional approach of using a fixed classifier in adversarial environments is generally Pareto suboptimal. Finally, we validate such conclusions on both synthetic and real-world classification problems. Copyright 2014 ACM.

  12. 14 CFR 23.934 - Turbojet and turbofan engine thrust reverser systems tests.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Turbojet and turbofan engine thrust... CATEGORY AIRPLANES Powerplant General § 23.934 Turbojet and turbofan engine thrust reverser systems tests. Thrust reverser systems of turbojet or turbofan engines must meet the requirements of § 33.97 of this...

  13. Engineering biological systems toward a sustainable bioeconomy.

    Science.gov (United States)

    Lopes, Mateus Schreiner Garcez

    2015-06-01

    The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy.

  14. Engineering Liposomes and Nanoparticles for Biological Targeting

    DEFF Research Database (Denmark)

    Jølck, Rasmus Irming; Feldborg, Lise Nørkjær; Andersen, Simon

    2011-01-01

    Our ability to engineer nanomaterials for biological and medical applications is continuously increasing, and nanomaterial designs are becoming more and more complex. One very good example of this is the drug delivery field where nanoparticle systems can be used to deliver drugs specifically...... to diseased tissue. In the early days, the design of the nanoparticles was relatively simple, but today we can surface functionalize and manipulate material properties to target diseased tissue and build highly complex drug release mechanisms into our designs. One of the most promising strategies in drug...

  15. Smartphone based scalable reverse engineering by digital image correlation

    Science.gov (United States)

    Vidvans, Amey; Basu, Saurabh

    2018-03-01

    There is a need for scalable open source 3D reconstruction systems for reverse engineering. This is because most commercially available reconstruction systems are capital and resource intensive. To address this, a novel reconstruction technique is proposed. The technique involves digital image correlation based characterization of surface speeds followed by normalization with respect to angular speed during rigid body rotational motion of the specimen. Proof of concept of the same is demonstrated and validated using simulation and empirical characterization. Towards this, smart-phone imaging and inexpensive off the shelf components along with those fabricated additively using poly-lactic acid polymer with a standard 3D printer are used. Some sources of error in this reconstruction methodology are discussed. It is seen that high curvatures on the surface suppress accuracy of reconstruction. Reasons behind this are delineated in the nature of the correlation function. Theoretically achievable resolution during smart-phone based 3D reconstruction by digital image correlation is derived.

  16. [Veneer computer aided design based on reverse engineering technology].

    Science.gov (United States)

    Liu, Ming-li; Chen, Xiao-dong; Wang, Yong

    2012-03-01

    To explore the computer aided design (CAD) method of veneer restoration, and to assess if the solution can help prosthesis meet morphology esthetics standard. A volunteer's upper right central incisor needed to be restored with veneer. Super hard stone models of patient's dentition (before and after tooth preparation) were scanned with the three-dimensional laser scanner. The veneer margin was designed as butt-to-butt type. The veneer was constructed using reverse engineering (RE) software. The technique guideline of veneers CAD was explore based on RE software, and the veneers was smooth, continuous and symmetrical, which met esthetics construction needs. It was a feasible method to reconstruct veneer restoration based on RE technology.

  17. Automatic Reverse Engineering of Private Flight Control Protocols of UAVs

    Directory of Open Access Journals (Sweden)

    Ran Ji

    2017-01-01

    Full Text Available The increasing use of civil unmanned aerial vehicles (UAVs has the potential to threaten public safety and privacy. Therefore, airspace administrators urgently need an effective method to regulate UAVs. Understanding the meaning and format of UAV flight control commands by automatic protocol reverse-engineering techniques is highly beneficial to UAV regulation. To improve our understanding of the meaning and format of UAV flight control commands, this paper proposes a method to automatically analyze the private flight control protocols of UAVs. First, we classify flight control commands collected from a binary network trace into clusters; then, we analyze the meaning of flight control commands by the accumulated error of each cluster; next, we extract the binary format of commands and infer field semantics in these commands; and finally, we infer the location of the check field in command and the generator polynomial matrix. The proposed approach is validated via experiments on a widely used consumer UAV.

  18. Update of GRASP/Ada reverse engineering tools for Ada

    Science.gov (United States)

    Cross, James H., II

    1993-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) successfully created and prototyped a new algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada PDL or source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional pretty printed Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype CSD generator (Version 1) was designed and implemented using FLEX and BISON running under VMS on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented using the HP widget toolkit and the X Windows System. In Phase 3, the user interface was extensively reworked using the Athena widget toolkit and X Windows. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. Following Phase 3,e two update phases were completed. Update'92 focused on the initial analysis of evaluation data collected from software engineering students at Auburn University and the addition of significant enhancements to the user interface. Update'93 (the current update) focused on the statistical analysis of the data collected in the previous update and preparation of Version 3.4 of the prototype for limited distribution to facilitate further evaluation. The current prototype provides the capability for the user to generate CSD's from Ada PDL or source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for practical

  19. Reversible S-nitrosylation in an engineered azurin

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Shiliang; Liu, Jing; Cowley, Ryan E.; Hosseinzadeh, Parisa; Marshall, Nicholas M.; Yu, Yang; Robinson, Howard; Nilges, Mark J.; Blackburn, Ninian J.; Solomon, Edward I.; Lu, Yi

    2016-04-25

    S-Nitrosothiols are known as reagents for NO storage and transportation and as regulators in many physiological processes. Although the S-nitrosylation catalysed by haem proteins is well known, no direct evidence of S-nitrosylation in copper proteins has been reported. Here, we report reversible insertion of NO into a copper–thiolate bond in an engineered copper centre in Pseudomonas aeruginosa azurin by rational design of the primary coordination sphere and tuning its reduction potential by deleting a hydrogen bond in the secondary coordination sphere. The results not only provide the first direct evidence of S-nitrosylation of Cu(II)-bound cysteine in metalloproteins, but also shed light on the reaction mechanism and structural features responsible for stabilizing the elusive Cu(I)–S(Cys)NO species. The fast, efficient and reversible S-nitrosylation reaction is used to demonstrate its ability to prevent NO inhibition of cytochrome bo3 oxidase activity by competing for NO binding with the native enzyme under physiologically relevant conditions.

  20. Modeling planarian regeneration: a primer for reverse-engineering the worm.

    Directory of Open Access Journals (Sweden)

    Daniel Lobo

    Full Text Available A mechanistic understanding of robust self-assembly and repair capabilities of complex systems would have enormous implications for basic evolutionary developmental biology as well as for transformative applications in regenerative biomedicine and the engineering of highly fault-tolerant cybernetic systems. Molecular biologists are working to identify the pathways underlying the remarkable regenerative abilities of model species that perfectly regenerate limbs, brains, and other complex body parts. However, a profound disconnect remains between the deluge of high-resolution genetic and protein data on pathways required for regeneration, and the desired spatial, algorithmic models that show how self-monitoring and growth control arise from the synthesis of cellular activities. This barrier to progress in the understanding of morphogenetic controls may be breached by powerful techniques from the computational sciences-using non-traditional modeling approaches to reverse-engineer systems such as planaria: flatworms with a complex bodyplan and nervous system that are able to regenerate any body part after traumatic injury. Currently, the involvement of experts from outside of molecular genetics is hampered by the specialist literature of molecular developmental biology: impactful collaborations across such different fields require that review literature be available that presents the key functional capabilities of important biological model systems while abstracting away from the often irrelevant and confusing details of specific genes and proteins. To facilitate modeling efforts by computer scientists, physicists, engineers, and mathematicians, we present a different kind of review of planarian regeneration. Focusing on the main patterning properties of this system, we review what is known about the signal exchanges that occur during regenerative repair in planaria and the cellular mechanisms that are thought to underlie them. By establishing an

  1. Un-Building Blocks: A Model of Reverse Engineering and Applicable Heuristics

    Science.gov (United States)

    2015-12-01

    Inclusion relationships of root events, events, and subevents .................179  Table 5.  Formal specification of reverse engineering model using Monterey...intend to stay technologically competitive at personal as well as societal levels. Third, reverse engineering is important for pedagogical reasons. It is...increasingly blurred (Anderson, 2012).4 Third, reverse engineering can be a pedagogical tool (Otto & Wood, 2000; O’Brien, 2010; Halsmer, 2013

  2. Internet-based dimensional verification system for reverse engineering processes

    International Nuclear Information System (INIS)

    Song, In Ho; Kim, Kyung Don; Chung, Sung Chong

    2008-01-01

    This paper proposes a design methodology for a Web-based collaborative system applicable to reverse engineering processes in a distributed environment. By using the developed system, design reviewers of new products are able to confirm geometric shapes, inspect dimensional information of products through measured point data, and exchange views with other design reviewers on the Web. In addition, it is applicable to verifying accuracy of production processes by manufacturing engineers. Functional requirements for designing this Web-based dimensional verification system are described in this paper. ActiveX-server architecture and OpenGL plug-in methods using ActiveX controls realize the proposed system. In the developed system, visualization and dimensional inspection of the measured point data are done directly on the Web: conversion of the point data into a CAD file or a VRML form is unnecessary. Dimensional verification results and design modification ideas are uploaded to markups and/or XML files during collaboration processes. Collaborators review the markup results created by others to produce a good design result on the Web. The use of XML files allows information sharing on the Web to be independent of the platform of the developed system. It is possible to diversify the information sharing capability among design collaborators. Validity and effectiveness of the developed system has been confirmed by case studies

  3. Internet-based dimensional verification system for reverse engineering processes

    Energy Technology Data Exchange (ETDEWEB)

    Song, In Ho [Ajou University, Suwon (Korea, Republic of); Kim, Kyung Don [Small Business Corporation, Suwon (Korea, Republic of); Chung, Sung Chong [Hanyang University, Seoul (Korea, Republic of)

    2008-07-15

    This paper proposes a design methodology for a Web-based collaborative system applicable to reverse engineering processes in a distributed environment. By using the developed system, design reviewers of new products are able to confirm geometric shapes, inspect dimensional information of products through measured point data, and exchange views with other design reviewers on the Web. In addition, it is applicable to verifying accuracy of production processes by manufacturing engineers. Functional requirements for designing this Web-based dimensional verification system are described in this paper. ActiveX-server architecture and OpenGL plug-in methods using ActiveX controls realize the proposed system. In the developed system, visualization and dimensional inspection of the measured point data are done directly on the Web: conversion of the point data into a CAD file or a VRML form is unnecessary. Dimensional verification results and design modification ideas are uploaded to markups and/or XML files during collaboration processes. Collaborators review the markup results created by others to produce a good design result on the Web. The use of XML files allows information sharing on the Web to be independent of the platform of the developed system. It is possible to diversify the information sharing capability among design collaborators. Validity and effectiveness of the developed system has been confirmed by case studies

  4. GRASP/Ada 95: Reverse Engineering Tools for Ada

    Science.gov (United States)

    Cross, James H., II

    1996-01-01

    The GRASP/Ada project (Graphical Representations of Algorithms, Structures, and Processes for Ada) has successfully created and prototyped an algorithmic level graphical representation for Ada software, the Control Structure Diagram (CSD), and a new visualization for a fine-grained complexity metric called the Complexity Profile Graph (CPG). By synchronizing the CSD and the CPG, the CSD view of control structure, nesting, and source code is directly linked to the corresponding visualization of statement level complexity in the CPG. GRASP has been integrated with GNAT, the GNU Ada 95 Translator to provide a comprehensive graphical user interface and development environment for Ada 95. The user may view, edit, print, and compile source code as a CSD with no discernible addition to storage or computational overhead. The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and, as a result, improve reliability and reduce costs. The emphasis has been on the automatic generation of the CSD from Ada 95 source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. The current update has focused on the design and implementation of a new Motif compliant user interface, and a new CSD generator consisting of a tagger and renderer. The Complexity Profile Graph (CPG) is based on a set of functions that describes the context, content, and the scaling for complexity on a statement by statement basis. When combined graphicafly, the result is a composite profile of complexity for the program unit. Ongoing research includes the development and refinement of the associated functions, and the development of the CPG generator prototype. The current Version 5.0 prototype provides the capability for the user to generate CSDs and CPGs from Ada 95 source code in a reverse engineering as well as forward engineering mode with a level of flexibility suitable for

  5. Neutron tomography as a reverse engineering method applied to the IS-60 Rover gas turbine

    CSIR Research Space (South Africa)

    Roos, TH

    2011-09-01

    Full Text Available Probably the most common method of reverse engineering in mechanical engineering involves measuring the physical geometry of a component using a coordinate measuring machine (CMM). Neutron tomography, in contrast, is used primarily as a non...

  6. Engineering and Biology: Counsel for a Continued Relationship

    Science.gov (United States)

    Levy, Arnon; Siegal, Mark L.; Soyer, Orkun S.; Wagner, Andreas

    2015-01-01

    Biologists frequently draw on ideas and terminology from engineering. Evolutionary systems biology—with its circuits, switches, and signal processing—is no exception. In parallel with the frequent links drawn between biology and engineering, there is ongoing criticism against this cross-fertilization, using the argument that over-simplistic metaphors from engineering are likely to mislead us as engineering is fundamentally different from biology. In this article, we clarify and reconfigure the link between biology and engineering, presenting it in a more favorable light. We do so by, first, arguing that critics operate with a narrow and incorrect notion of how engineering actually works, and of what the reliance on ideas from engineering entails. Second, we diagnose and diffuse one significant source of concern about appeals to engineering, namely that they are inherently and problematically metaphorical. We suggest that there is plenty of fertile ground left for a continued, healthy relationship between engineering and biology. PMID:26085824

  7. [Are there pseudophototropic reactions in biology? Part 4: On the reversibility of biologic/synthetic polymere systems (author's transl)].

    Science.gov (United States)

    Patschorke, J

    1979-01-01

    In further research on pseudophototropic behaviour in cellular membranes of halobacteria the reversibility of vinylmethylethermaleic anhydride-copolymeres with biological liquids is tested and the basic principles of different colour generating reactions are studied.

  8. Reverse Engineering Nature to Design Biomimetic Total Knee Implants.

    Science.gov (United States)

    Varadarajan, Kartik Mangudi; Zumbrunn, Thomas; Rubash, Harry E; Malchau, Henrik; Muratoglu, Orhun K; Li, Guoan

    2015-10-01

    While contemporary total knee arthroplasty (TKA) provides tremendous clinical benefits, the normal feel and function of the knee is not fully restored. To address this, a novel design process was developed to reverse engineer "biomimetic" articular surfaces that are compatible with normal soft-tissue envelope and kinematics of the knee. The biomimetic articular surface is created by moving the TKA femoral component along in vivo kinematics of normal knees and carving out the tibial articular surface from a rectangular tibial block. Here, we describe the biomimetic design process. In addition, we utilize geometric comparisons and kinematic simulations to show that; (1) tibial articular surfaces of conventional implants are fundamentally incompatible with normal knee motion, and (2) the anatomic geometry of the biomimetic surface contributes directly to restoration of normal knee kinematics. Such biomimetic implants may enable us to achieve the long sought after goal of a "normal" knee post-TKA surgery. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    Science.gov (United States)

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

  10. Chemical respiratory allergy: Reverse engineering an adverse outcome pathway

    International Nuclear Information System (INIS)

    Kimber, Ian; Dearman, Rebecca J.; Basketter, David A.; Boverhof, Darrell R.

    2014-01-01

    Allergic sensitisation of the respiratory tract by chemicals is associated with rhinitis and asthma and remains an important occupational health issue. Although less than 80 chemicals have been confirmed as respiratory allergens the adverse health effects can be serious, and in rare instances can be fatal, and there are, in addition, related socioeconomic issues. The challenges that chemical respiratory allergy pose for toxicologists are substantial. No validated methods are available for hazard identification and characterisation, and this is due in large part to the fact that there remains considerable uncertainty and debate about the mechanisms through which sensitisation of the respiratory tract is acquired. Despite that uncertainty, there is a need to establish some common understanding of the key events and processes that are involved in respiratory sensitisation to chemicals and that might in turn provide the foundations for novel approaches to safety assessment. In recent years the concept of adverse outcome pathways (AOP) has gained some considerable interest among the toxicology community as a basis for outlining the key steps leading to an adverse health outcome, while also providing a framework for focusing future research, and for developing alternative paradigms for hazard characterisation. Here we explore application of the same general principles to an examination of the induction by chemicals of respiratory sensitisation. In this instance, however, we have chosen to adopt a reverse engineering approach and to model a possible AOP for chemical respiratory allergy working backwards from the elicitation of adverse health effects to the cellular and molecular mechanisms that are implicated in the acquisition of sensitisation

  11. Laser marking as a result of applying reverse engineering

    Science.gov (United States)

    Mihalache, Andrei; Nagîţ, Gheorghe; Rîpanu, Marius Ionuţ; Slǎtineanu, Laurenţiu; Dodun, Oana; Coteaţǎ, Margareta

    2018-05-01

    The elaboration of a modern manufacturing technology needs a certain quantum of information concerning the part to be obtained. When it is necessary to elaborate the technology for an existing object, such an information could be ensured by using the principles specific to the reverse engineering. Essentially, in the case of this method, the analysis of the surfaces and of other characteristics of the part must offer enough information for the elaboration of the part manufacturing technology. On the other hand, it is known that the laser marking is a processing method able to ensure the transfer of various inscriptions or drawings on a part. Sometimes, the laser marking could be based on the analysis of an existing object, whose image could be used to generate the same object or an improved object. There are many groups of factors able to affect the results of applying the laser marking process. A theoretical analysis was proposed to show that the heights of triangles obtained by means of a CNC marking equipment depend on the width of the line generated by the laser spot on the workpiece surface. An experimental research was thought and materialized to highlight the influence exerted by the line with and the angle of lines intersections on the accuracy of the marking process. By mathematical processing of the experimental results, empirical mathematical models were determined. The power type model and the graphical representation elaborated on the base of this model offered an image concerning the influences exerted by the considered input factors on the marking process accuracy.

  12. Experimental study of a reverse flow catalytic converter for a duel fuel engine

    Energy Technology Data Exchange (ETDEWEB)

    Liu, B.; Checkel, M. D. [Alberta Univ., Dept. of Mechanical Engineering, Edmonton, ANB (Canada); Hayes, R. E. [Alberta Univ., Dept, of Chemical and Materials Engineering, Edmonton, AB, (Canada)

    2001-08-01

    Performance of a reverse flow catalytic converter for a methane/diesel dual fuel engine is evaluated under steady and transient engine conditions. The converter is of the monolith honeycomb type with palladium catalyst washcoat. Results of the reverse flow converter's performance was found to be superior for several steady state engine operations when compared to unidirectional flow operation. In transient operations following a step change in engine operating conditions, reverse flow was found to be better than unidirectional flow when the change in engine operation was such as to reduce the exhaust gas temperature. When exhaust gas temperature was increased, reverse flow decreased the rate of increase in the reactor temperature. Testing was done using the transient Japanese 6-Mode tests. Best results were achieved with a switch time in the five seconds to fifteen seconds range. 31 refs., 9 tabs., 24 figs.

  13. Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

    in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

  14. Challenges and opportunities in synthetic biology for chemical engineers.

    Science.gov (United States)

    Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

    2013-11-15

    Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement.

  15. Challenges and opportunities in synthetic biology for chemical engineers

    Science.gov (United States)

    Luo, Yunzi; Lee, Jung-Kul; Zhao, Huimin

    2012-01-01

    Synthetic biology provides numerous great opportunities for chemical engineers in the development of new processes for large-scale production of biofuels, value-added chemicals, and protein therapeutics. However, challenges across all scales abound. In particular, the modularization and standardization of the components in a biological system, so-called biological parts, remain the biggest obstacle in synthetic biology. In this perspective, we will discuss the main challenges and opportunities in the rapidly growing synthetic biology field and the important roles that chemical engineers can play in its advancement. PMID:24222925

  16. International Conference on Medical and Biological Engineering 2017

    CERN Document Server

    2017-01-01

    This volume presents the proceedings of the International Conference on Medical and Biological Engineering held from 16 to 18 March 2017 in Sarajevo, Bosnia and Herzegovina. Focusing on the theme of ‘Pursuing innovation. Shaping the future’, it highlights the latest advancements in Biomedical Engineering and also presents the latest findings, innovative solutions and emerging challenges in this field. Topics include: - Biomedical Signal Processing - Biomedical Imaging and Image Processing - Biosensors and Bioinstrumentation - Bio-Micro/Nano Technologies - Biomaterials - Biomechanics, Robotics and Minimally Invasive Surgery - Cardiovascular, Respiratory and Endocrine Systems Engineering - Neural and Rehabilitation Engineering - Molecular, Cellular and Tissue Engineering - Bioinformatics and Computational Biology - Clinical Engineering and Health Technology Assessment - Health Informatics, E-Health and Telemedicine - Biomedical Engineering Education - Pharmaceutical Engineering.

  17. IntegromeDB: an integrated system and biological search engine.

    Science.gov (United States)

    Baitaluk, Michael; Kozhenkov, Sergey; Dubinina, Yulia; Ponomarenko, Julia

    2012-01-19

    With the growth of biological data in volume and heterogeneity, web search engines become key tools for researchers. However, general-purpose search engines are not specialized for the search of biological data. Here, we present an approach at developing a biological web search engine based on the Semantic Web technologies and demonstrate its implementation for retrieving gene- and protein-centered knowledge. The engine is available at http://www.integromedb.org. The IntegromeDB search engine allows scanning data on gene regulation, gene expression, protein-protein interactions, pathways, metagenomics, mutations, diseases, and other gene- and protein-related data that are automatically retrieved from publicly available databases and web pages using biological ontologies. To perfect the resource design and usability, we welcome and encourage community feedback.

  18. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Directory of Open Access Journals (Sweden)

    Bor-Sen Chen

    2013-10-01

    Full Text Available Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering.

  19. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    Science.gov (United States)

    Chen, Bor-Sen; Wu, Chia-Chou

    2013-01-01

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of stability, robustness, and transduction ability through system identification, and through system analysis methods; (iii) system control methods at different levels of biological networks, which provide an understanding of systematic mechanisms to robustly control system states, minimize malfunctions, and provide potential therapeutic targets in disease treatment; (iv) systematic design methods for the modification and construction of biological networks with desired behaviors, which provide system design principles and system simulations for synthetic biology designs and systems metabolic engineering. This review describes current developments in systems biology, systems synthetic biology, and systems metabolic engineering for engineering and biology researchers. We also discuss challenges and future prospects for systems biology and the concept of systems biology as an integrated platform for bioinformatics, systems synthetic biology, and systems metabolic engineering. PMID:24709875

  20. Penerapan Reverse Engineering Dalam Penentuan Pola Interaksi Sequence Diagram Pada Sampel Aplikasi Android

    Directory of Open Access Journals (Sweden)

    Vierdy Sulfianto Rahmadani

    2015-04-01

    Full Text Available The purpose of this research is to apply the application of reverse engineering to determine interaction patterns of the Sequence diagram that can be used by system analysts as a template for designing UML sequence diagrams. Sample applications from android are used as dataset for reverse engineering and pattern identification. The first step is collecting application datasets. The next stage is identifying the features and applications activity, reverse engineering to obtain a sequence diagram model, and then synthesize all of the models into an interaction pattern of sequence diagram. The final step is to test the patterns by implementing it in an application development case stud. The evaluation results concludes that interaction patterns of sequence diagram designs obtained in reverse engineering steps is able to be implemented in software development that contained similar features with the obtained features in this research.

  1. Threshold-Dependent Camouflaged Cells to Secure Circuits Against Reverse Engineering Attacks

    OpenAIRE

    Collantes, Maria I. Mera; Massad, Mohamed El; Garg, Siddharth

    2016-01-01

    With current tools and technology, someone who has physical access to a chip can extract the detailed layout of the integrated circuit (IC). By using advanced visual imaging techniques, reverse engineering can reveal details that are meant to be kept secret, such as a secure protocol or novel implementation that offers a competitive advantage. A promising solution to defend against reverse engineering attacks is IC camouflaging. In this work, we propose a new camouflaging technique based on t...

  2. Reverse engineering by design: using history to teach.

    Science.gov (United States)

    Fagette, Paul

    2013-01-01

    Engineering students rarely have an opportunity to delve into the historic antecedents of design in their craft, and this is especially true for biomedical devices. The teaching emphasis is always on the new, the innovative, and the future. Even so, over the last decade, I have coupled a research agenda with engineering special projects into a successful format that allows young biomedical engineering students to understand aspects of their history and learn the complexities of design. There is value in having knowledge of historic engineering achievements, not just for an appreciation of these accomplishments but also for understanding exactly how engineers and clinicians of the day executed their feats-in other words, how the design process works. Ultimately, this particular educational odyssey confirms that history and engineering education are not only compatible but mutually supportive.

  3. A Process Re-engineering Framework for Reverse Logistics based on a Case Study

    Directory of Open Access Journals (Sweden)

    Hing Kai Chan

    2010-09-01

    Full Text Available Reverse logistics has gained increasing attention in recent years as a channel for companies to achieve operational excellence. The process involves manipulation of returned materials, or even products, which forms a pivotal role in sustainable development throughout the whole supply chains. To make reverse logistics possible, process re-engineering may need to be carried out. However, the processes involved in reengineering are practically complicated. Objectives, benefits, and applicability of any process re-engineering require a careful and detailed strategic planning. This paper aims to propose an easy-to-follow step-by-step framework for practitioners to perform process re-engineering, to learn and identify the critical issues in each step, and to be successful in applying process re-engineering in order to enhance reverse logistics performance. A learner-centred approach is adopted based on a case study of process re-engineering, which is demonstrated in the paper for explanation.

  4. Advancing metabolic engineering through systems biology of industrial microorganisms.

    Science.gov (United States)

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

    Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Advancing metabolic engineering through systems biology of industrial microorganisms

    DEFF Research Database (Denmark)

    Dai, Zongjie; Nielsen, Jens

    2015-01-01

    resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review......Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable...... the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further....

  6. Macromolecular cell surface engineering for accelerated and reversible cellular aggregation.

    OpenAIRE

    Amaral, A. J.; Pasparakis, G.

    2015-01-01

    We report the synthesis of two simple copolymers that induce rapid cell aggregation within minutes in a fully reversible manner. The polymers can act as self-supporting "cellular glues" or as "drivers" of 3D cell spheroids/aggregates formation at minute concentrations.

  7. Reverse-engineering of gene networks for regulating early blood development from single-cell measurements.

    Science.gov (United States)

    Wei, Jiangyong; Hu, Xiaohua; Zou, Xiufen; Tian, Tianhai

    2017-12-28

    Recent advances in omics technologies have raised great opportunities to study large-scale regulatory networks inside the cell. In addition, single-cell experiments have measured the gene and protein activities in a large number of cells under the same experimental conditions. However, a significant challenge in computational biology and bioinformatics is how to derive quantitative information from the single-cell observations and how to develop sophisticated mathematical models to describe the dynamic properties of regulatory networks using the derived quantitative information. This work designs an integrated approach to reverse-engineer gene networks for regulating early blood development based on singel-cell experimental observations. The wanderlust algorithm is initially used to develop the pseudo-trajectory for the activities of a number of genes. Since the gene expression data in the developed pseudo-trajectory show large fluctuations, we then use Gaussian process regression methods to smooth the gene express data in order to obtain pseudo-trajectories with much less fluctuations. The proposed integrated framework consists of both bioinformatics algorithms to reconstruct the regulatory network and mathematical models using differential equations to describe the dynamics of gene expression. The developed approach is applied to study the network regulating early blood cell development. A graphic model is constructed for a regulatory network with forty genes and a dynamic model using differential equations is developed for a network of nine genes. Numerical results suggests that the proposed model is able to match experimental data very well. We also examine the networks with more regulatory relations and numerical results show that more regulations may exist. We test the possibility of auto-regulation but numerical simulations do not support the positive auto-regulation. In addition, robustness is used as an importantly additional criterion to select candidate

  8. Synthetic biology and its alternatives. Descartes, Kant and the idea of engineering biological machines.

    Science.gov (United States)

    Kogge, Werner; Richter, Michael

    2013-06-01

    The engineering-based approach of synthetic biology is characterized by an assumption that 'engineering by design' enables the construction of 'living machines'. These 'machines', as biological machines, are expected to display certain properties of life, such as adapting to changing environments and acting in a situated way. This paper proposes that a tension exists between the expectations placed on biological artefacts and the notion of producing such systems by means of engineering; this tension makes it seem implausible that biological systems, especially those with properties characteristic of living beings, can in fact be produced using the specific methods of engineering. We do not claim that engineering techniques have nothing to contribute to the biotechnological construction of biological artefacts. However, drawing on Descartes's and Kant's thinking on the relationship between the organism and the machine, we show that it is considerably more plausible to assume that distinctively biological artefacts emerge within a paradigm different from the paradigm of the Cartesian machine that underlies the engineering approach. We close by calling for increased attention to be paid to approaches within molecular biology and chemistry that rest on conceptions different from those of synthetic biology's engineering paradigm. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Introduction to bioengineering: melding of engineering and biological sciences.

    Science.gov (United States)

    Shoureshi, Rahmat A

    2005-04-01

    Engineering has traditionally focused on the external extensions of organisms, such as transportation systems, high-rise buildings, and entertainment systems. In contrast, bioengineering is concerned with inward processes of biologic organisms. Utilization of engineering principles and techniques in the analysis and solution of problems in medicine and biology is the basis for bioengineering. This article discusses subspecialties in bioengineering and presents examples of projects in this discipline.

  10. RegnANN: Reverse Engineering Gene Networks using Artificial Neural Networks.

    Directory of Open Access Journals (Sweden)

    Marco Grimaldi

    Full Text Available RegnANN is a novel method for reverse engineering gene networks based on an ensemble of multilayer perceptrons. The algorithm builds a regressor for each gene in the network, estimating its neighborhood independently. The overall network is obtained by joining all the neighborhoods. RegnANN makes no assumptions about the nature of the relationships between the variables, potentially capturing high-order and non linear dependencies between expression patterns. The evaluation focuses on synthetic data mimicking plausible submodules of larger networks and on biological data consisting of submodules of Escherichia coli. We consider Barabasi and Erdös-Rényi topologies together with two methods for data generation. We verify the effect of factors such as network size and amount of data to the accuracy of the inference algorithm. The accuracy scores obtained with RegnANN is methodically compared with the performance of three reference algorithms: ARACNE, CLR and KELLER. Our evaluation indicates that RegnANN compares favorably with the inference methods tested. The robustness of RegnANN, its ability to discover second order correlations and the agreement between results obtained with this new methods on both synthetic and biological data are promising and they stimulate its application to a wider range of problems.

  11. Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

    Science.gov (United States)

    Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

    1998-01-01

    Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.

  12. Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering

    Science.gov (United States)

    Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland

    2000-01-01

    Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.

  13. Challenges of medical and biological engineering and science

    Energy Technology Data Exchange (ETDEWEB)

    Magjarevic, R [University of Zagreb, Faculty of Electrical Engineering and Computing, Zagreb (Croatia)

    2004-07-01

    All aspects of biomedical engineering and science, from research and development, education and training, implementation in health care systems, internationalisation and globalisation, and other, new issues are present in the strategy and in action plans of the International Federation for Medical and Biological Engineering (IFMBE) which, with help of a large number of highly motivated volunteers, will stay in leading position in biomedical engineering and science.

  14. Challenges of medical and biological engineering and science

    International Nuclear Information System (INIS)

    Magjarevic, R.

    2004-01-01

    All aspects of biomedical engineering and science, from research and development, education and training, implementation in health care systems, internationalisation and globalisation, and other, new issues are present in the strategy and in action plans of the International Federation for Medical and Biological Engineering (IFMBE) which, with help of a large number of highly motivated volunteers, will stay in leading position in biomedical engineering and science

  15. Synthetic Biology: Engineering Living Systems from Biophysical Principles.

    Science.gov (United States)

    Bartley, Bryan A; Kim, Kyung; Medley, J Kyle; Sauro, Herbert M

    2017-03-28

    Synthetic biology was founded as a biophysical discipline that sought explanations for the origins of life from chemical and physical first principles. Modern synthetic biology has been reinvented as an engineering discipline to design new organisms as well as to better understand fundamental biological mechanisms. However, success is still largely limited to the laboratory and transformative applications of synthetic biology are still in their infancy. Here, we review six principles of living systems and how they compare and contrast with engineered systems. We cite specific examples from the synthetic biology literature that illustrate these principles and speculate on their implications for further study. To fully realize the promise of synthetic biology, we must be aware of life's unique properties. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. Recent applications of synthetic biology tools for yeast metabolic engineering

    DEFF Research Database (Denmark)

    Jensen, Michael Krogh; Keasling, Jay

    2015-01-01

    to engineer microbial chemical factories has steadily decreased, improvement is still needed. Through the development of synthetic biology tools for key microbial hosts, it should be possible to further decrease the development times and improve the reliability of the resulting microorganism. Together...... with continuous decreases in price and improvements in DNA synthesis, assembly and sequencing, synthetic biology tools will rationalize time-consuming strain engineering, improve control of metabolic fluxes, and diversify screening assays for cellular metabolism. This review outlines some recently developed...... synthetic biology tools and their application to improve production of chemicals and fuels in yeast. Finally, we provide a perspective for the challenges that lie ahead....

  17. XIV Mediterranean Conference on Medical and Biological Engineering and Computing

    CERN Document Server

    Christofides, Stelios; Pattichis, Constantinos

    2016-01-01

    This volume presents the proceedings of Medicon 2016, held in Paphos, Cyprus. Medicon 2016 is the XIV in the series of regional meetings of the International Federation of Medical and Biological Engineering (IFMBE) in the Mediterranean. The goal of Medicon 2016 is to provide updated information on the state of the art on Medical and Biological Engineering and Computing under the main theme “Systems Medicine for the Delivery of Better Healthcare Services”. Medical and Biological Engineering and Computing cover complementary disciplines that hold great promise for the advancement of research and development in complex medical and biological systems. Research and development in these areas are impacting the science and technology by advancing fundamental concepts in translational medicine, by helping us understand human physiology and function at multiple levels, by improving tools and techniques for the detection, prevention and treatment of disease. Medicon 2016 provides a common platform for the cross fer...

  18. An approach for reduction of false predictions in reverse engineering of gene regulatory networks.

    Science.gov (United States)

    Khan, Abhinandan; Saha, Goutam; Pal, Rajat Kumar

    2018-05-14

    A gene regulatory network discloses the regulatory interactions amongst genes, at a particular condition of the human body. The accurate reconstruction of such networks from time-series genetic expression data using computational tools offers a stiff challenge for contemporary computer scientists. This is crucial to facilitate the understanding of the proper functioning of a living organism. Unfortunately, the computational methods produce many false predictions along with the correct predictions, which is unwanted. Investigations in the domain focus on the identification of as many correct regulations as possible in the reverse engineering of gene regulatory networks to make it more reliable and biologically relevant. One way to achieve this is to reduce the number of incorrect predictions in the reconstructed networks. In the present investigation, we have proposed a novel scheme to decrease the number of false predictions by suitably combining several metaheuristic techniques. We have implemented the same using a dataset ensemble approach (i.e. combining multiple datasets) also. We have employed the proposed methodology on real-world experimental datasets of the SOS DNA Repair network of Escherichia coli and the IMRA network of Saccharomyces cerevisiae. Subsequently, we have experimented upon somewhat larger, in silico networks, namely, DREAM3 and DREAM4 Challenge networks, and 15-gene and 20-gene networks extracted from the GeneNetWeaver database. To study the effect of multiple datasets on the quality of the inferred networks, we have used four datasets in each experiment. The obtained results are encouraging enough as the proposed methodology can reduce the number of false predictions significantly, without using any supplementary prior biological information for larger gene regulatory networks. It is also observed that if a small amount of prior biological information is incorporated here, the results improve further w.r.t. the prediction of true positives

  19. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    NARCIS (Netherlands)

    He, F.; Murabito, E.; Westerhoff, H.V.

    2016-01-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out throughin silicotheoretical studies with the aim to guide and complement furtherin vitroandin vivoexperimental

  20. Basic science through engineering? Synthetic modeling and the idea of biology-inspired engineering.

    Science.gov (United States)

    Knuuttila, Tarja; Loettgers, Andrea

    2013-06-01

    Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more "biology inspired." Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Reverse Flow Engine Core Having a Ducted Fan with Integrated Secondary Flow Blades

    Science.gov (United States)

    Kisska, Michael K. (Inventor); Princen, Norman H. (Inventor); Kuehn, Mark S. (Inventor); Cosentino, Gary B. (Inventor)

    2014-01-01

    Secondary air flow is provided for a ducted fan having a reverse flow turbine engine core driving a fan blisk. The fan blisk incorporates a set of thrust fan blades extending from an outer hub and a set of integral secondary flow blades extending intermediate an inner hub and the outer hub. A nacelle provides an outer flow duct for the thrust fan blades and a secondary flow duct carries flow from the integral secondary flow blades as cooling air for components of the reverse flow turbine engine.

  2. Altering Height Data by Using Natural Logarithm as 3D Modelling Function for Reverse Engineering Application

    Science.gov (United States)

    Ilham Aminullah Abdulqawi, Nur; Salman Abu Mansor, Mohd

    2018-01-01

    The raw data extracted from reverse engineering based on vision mostly do not resemble the actual geometrical representation yet. Even though the higher object surface reflected the most visible light towards the camera and yield higher number of value based on Lambertian illumination model, this does not mean the curvature profile are always accurate. After all, there are many mathematical models to shape curvature profiles into the correct representation. However, one of the most appropriate models found is the natural logarithm function. The function itself has alteration properties towards the raw data generated from reverse engineering based on vision.

  3. Tissue Engineering Organs for Space Biology Research

    Science.gov (United States)

    Vandenburgh, H. H.; Shansky, J.; DelTatto, M.; Lee, P.; Meir, J.

    1999-01-01

    Long-term manned space flight requires a better understanding of skeletal muscle atrophy resulting from microgravity. Atrophy most likely results from changes at both the systemic level (e.g. decreased circulating growth hormone, increased circulating glucocorticoids) and locally (e.g. decreased myofiber resting tension). Differentiated skeletal myofibers in tissue culture have provided a model system over the last decade for gaining a better understanding of the interactions of exogenous growth factors, endogenous growth factors, and muscle fiber tension in regulating protein turnover rates and muscle cell growth. Tissue engineering these cells into three dimensional bioartificial muscle (BAM) constructs has allowed us to extend their use to Space flight studies for the potential future development of countermeasures.

  4. Compact Reversed-Field Pinch Reactors (CRFPR): preliminary engineering considerations

    International Nuclear Information System (INIS)

    Hagenson, R.L.; Krakowski, R.A.; Bathke, C.G.; Miller, R.L.; Embrechts, M.J.; Schnurr, N.M.; Battat, M.E.; LaBauve, R.J.; Davidson, J.W.

    1984-08-01

    The unique confinement physics of the Reversed-Field Pinch (RFP) projects to a compact, high-power-density fusion reactor that promises a significant reduction in the cost of electricity. The compact reactor also promises a factor-of-two reduction in the fraction of total cost devoted to the reactor plant equipment [i.e., fusion power core (FPC) plus support systems]. In addition to operational and developmental benefits, these physically smaller systems can operate economically over a range of total power output. After giving an extended background and rationale for the compact fusion approaches, key FPC subsystems for the Compact RFP Reactor (CRFPR) are developed, designed, and integrated for a minimum-cost, 1000-MWe(net) system. Both the problems and promise of the compact, high-power-density fusion reactor are quantitatively evaluated on the basis of this conceptual design. The material presented in this report both forms a framework for a broader, more expanded conceptual design as well as suggests directions and emphases for related research and development

  5. Multifunctional guest-host particles engineered by reversal nanoimprint lithography

    Science.gov (United States)

    Ha, Uh-Myong; Kaban, Burhan; Tomita, Andreea; Krekić, Kristijan; Klintuch, Dieter; Pietschnig, Rudolf; Ehresmann, Arno; Holzinger, Dennis; Hillmer, Hartmut

    2018-03-01

    Particulate polymeric microfibers with incorporated europium(III)oxide (Eu2O3) nanoparticles were introduced as a magneto-photoluminescent multifunctional material fabricated via reversal nanoimprint lithography. To specifically address the volume properties of these guest-host particles, the guest, Eu2O3, was milled down to an average particle size of 350 nm in diameter and mixed with the host-polymer, AMONIL®, before in situ hardening in the imprint stamp. The variation of the fabrication process parameters, i.e. delay time, spin coating speed, as well as the concentration of Eu2O3 nanoparticles was proven to have a significant impact on both the structure quality and the stamp release of the microfibers with respect to the formation of a thinner residual layer. Structural characterization performed by SEM revealed optimum fabrication process parameters for a homogeneous spatial distribution of Eu2O3 nanoparticles within the microfibers while simultaneously avoiding the formation of undesired agglomerates. The magneto-photoluminescent properties of Eu2O3 nanoparticles, i.e. a red emission at 613 nm and a paramagnetic response, were found to be superimposed to the optic and the diamagnetic behaviors of AMONIL®. The results imply that guest-host interdependence of these properties can be excluded and that the suggested technique enables for specific tailoring of particulate multifunctional materials with focus on their volume properties.

  6. Transcription control engineering and applications in synthetic biology

    Directory of Open Access Journals (Sweden)

    Michael D. Engstrom

    2017-09-01

    Full Text Available In synthetic biology, researchers assemble biological components in new ways to produce systems with practical applications. One of these practical applications is control of the flow of genetic information (from nucleic acid to protein, a.k.a. gene regulation. Regulation is critical for optimizing protein (and therefore activity levels and the subsequent levels of metabolites and other cellular properties. The central dogma of molecular biology posits that information flow commences with transcription, and accordingly, regulatory tools targeting transcription have received the most attention in synthetic biology. In this mini-review, we highlight many past successes and summarize the lessons learned in developing tools for controlling transcription. In particular, we focus on engineering studies where promoters and transcription terminators (cis-factors were directly engineered and/or isolated from DNA libraries. We also review several well-characterized transcription regulators (trans-factors, giving examples of how cis- and trans-acting factors have been combined to create digital and analogue switches for regulating transcription in response to various signals. Last, we provide examples of how engineered transcription control systems have been used in metabolic engineering and more complicated genetic circuits. While most of our mini-review focuses on the well-characterized bacterium Escherichia coli, we also provide several examples of the use of transcription control engineering in non-model organisms. Similar approaches have been applied outside the bacterial kingdom indicating that the lessons learned from bacterial studies may be generalized for other organisms.

  7. Transcription control engineering and applications in synthetic biology.

    Science.gov (United States)

    Engstrom, Michael D; Pfleger, Brian F

    2017-09-01

    In synthetic biology, researchers assemble biological components in new ways to produce systems with practical applications. One of these practical applications is control of the flow of genetic information (from nucleic acid to protein), a.k.a. gene regulation. Regulation is critical for optimizing protein (and therefore activity) levels and the subsequent levels of metabolites and other cellular properties. The central dogma of molecular biology posits that information flow commences with transcription, and accordingly, regulatory tools targeting transcription have received the most attention in synthetic biology. In this mini-review, we highlight many past successes and summarize the lessons learned in developing tools for controlling transcription. In particular, we focus on engineering studies where promoters and transcription terminators ( cis -factors) were directly engineered and/or isolated from DNA libraries. We also review several well-characterized transcription regulators ( trans- factors), giving examples of how cis- and trans -acting factors have been combined to create digital and analogue switches for regulating transcription in response to various signals. Last, we provide examples of how engineered transcription control systems have been used in metabolic engineering and more complicated genetic circuits. While most of our mini-review focuses on the well-characterized bacterium Escherichia coli , we also provide several examples of the use of transcription control engineering in non-model organisms. Similar approaches have been applied outside the bacterial kingdom indicating that the lessons learned from bacterial studies may be generalized for other organisms.

  8. Biological augmentation and tissue engineering approaches in meniscus surgery.

    Science.gov (United States)

    Moran, Cathal J; Busilacchi, Alberto; Lee, Cassandra A; Athanasiou, Kyriacos A; Verdonk, Peter C

    2015-05-01

    The purpose of this review was to evaluate the role of biological augmentation and tissue engineering strategies in meniscus surgery. Although clinical (human), preclinical (animal), and in vitro tissue engineering studies are included here, we have placed additional focus on addressing preclinical and clinical studies reported during the 5-year period used in this review in a systematic fashion while also providing a summary review of some important in vitro tissue engineering findings in the field over the past decade. A search was performed on PubMed for original works published from 2009 to March 31, 2014 using the term "meniscus" with all the following terms: "scaffolds," "constructs," "cells," "growth factors," "implant," "tissue engineering," and "regenerative medicine." Inclusion criteria were the following: English-language articles and original clinical, preclinical (in vivo), and in vitro studies of tissue engineering and regenerative medicine application in knee meniscus lesions published from 2009 to March 31, 2014. Three clinical studies and 18 preclinical studies were identified along with 68 tissue engineering in vitro studies. These reports show the increasing promise of biological augmentation and tissue engineering strategies in meniscus surgery. The role of stem cell and growth factor therapy appears to be particularly useful. A review of in vitro tissue engineering studies found a large number of scaffold types to be of promise for meniscus replacement. Limitations include a relatively low number of clinical or preclinical in vivo studies, in addition to the fact there is as yet no report in the literature of a tissue-engineered meniscus construct used clinically. Neither does the literature provide clarity on the optimal meniscus scaffold type or biological augmentation with which meniscus repair or replacement would be best addressed in the future. There is increasing focus on the role of mechanobiology and biomechanical and

  9. From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

    Science.gov (United States)

    Chiel, Hillel J.; McManus, Jeffrey M.; Shaw, Kendrick M.

    2010-01-01

    We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge…

  10. The fusion of biology, computer science, and engineering: towards efficient and successful synthetic biology.

    Science.gov (United States)

    Linshiz, Gregory; Goldberg, Alex; Konry, Tania; Hillson, Nathan J

    2012-01-01

    Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.

  11. ‘Can Simple Biological Systems be Built from Standardized Interchangeable Parts?’:Negotiating Biology and Engineering in a Synthetic Biology Competition

    OpenAIRE

    Frow, Emma; Calvert, Jane

    2013-01-01

    Synthetic biology represents a recent attempt to bring engineering principles and practices to working with biology. In practice, the nature of the relationship between engineering and biology in synthetic biology is a subject of ongoing debate. The disciplines of biology and engineering are typically seen to involve differentways of knowing and doing, and to embody different assumptions and objectives. Tensions between these approaches are playing out as the field of synthetic biology is bei...

  12. Understanding and Enhancing Soil Biological Health: The Solution for Reversing Soil Degradation

    Directory of Open Access Journals (Sweden)

    R. Michael Lehman

    2015-01-01

    Full Text Available Our objective is to provide an optimistic strategy for reversing soil degradation by increasing public and private research efforts to understand the role of soil biology, particularly microbiology, on the health of our world’s soils. We begin by defining soil quality/soil health (which we consider to be interchangeable terms, characterizing healthy soil resources, and relating the significance of soil health to agroecosystems and their functions. We examine how soil biology influences soil health and how biological properties and processes contribute to sustainability of agriculture and ecosystem services. We continue by examining what can be done to manipulate soil biology to: (i increase nutrient availability for production of high yielding, high quality crops; (ii protect crops from pests, pathogens, weeds; and (iii manage other factors limiting production, provision of ecosystem services, and resilience to stresses like droughts. Next we look to the future by asking what needs to be known about soil biology that is not currently recognized or fully understood and how these needs could be addressed using emerging research tools. We conclude, based on our perceptions of how new knowledge regarding soil biology will help make agriculture more sustainable and productive, by recommending research emphases that should receive first priority through enhanced public and private research in order to reverse the trajectory toward global soil degradation.

  13. CellNet: Network Biology Applied to Stem Cell Engineering

    Science.gov (United States)

    Cahan, Patrick; Li, Hu; Morris, Samantha A.; da Rocha, Edroaldo Lummertz; Daley, George Q.; Collins, James J.

    2014-01-01

    SUMMARY Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population, and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. PMID:25126793

  14. Methylcellulose Based Thermally Reversible Hydrogel System for Tissue Engineering Applications

    Directory of Open Access Journals (Sweden)

    Ram V. Devireddy

    2013-06-01

    Full Text Available The thermoresponsive behavior of a Methylcellulose (MC polymer was systematically investigated to determine its usability in constructing MC based hydrogel systems in cell sheet engineering applications. Solution-gel analyses were made to study the effects of polymer concentration, molecular weight and dissolved salts on the gelation of three commercially available MCs using differential scanning calorimeter and rheology. For investigation of the hydrogel stability and fluid uptake capacity, swelling and degradation experiments were performed with the hydrogel system exposed to cell culture solutions at incubation temperature for several days. From these experiments, the optimal composition of MC-water-salt that was able to produce stable hydrogels at or above 32 °C, was found to be 12% to 16% of MC (Mol. wt. of 15,000 in water with 0.5× PBS (~150mOsm. This stable hydrogel system was then evaluated for a week for its efficacy to support the adhesion and growth of specific cells in culture; in our case the stromal/stem cells derived from human adipose tissue derived stem cells (ASCs. The results indicated that the addition (evenly spread of ~200 µL of 2 mg/mL bovine collagen type -I (pH adjusted to 7.5 over the MC hydrogel surface at 37 °C is required to improve the ASC adhesion and proliferation. Upon confluence, a continuous monolayer ASC sheet was formed on the surface of the hydrogel system and an intact cell sheet with preserved cell–cell and cell–extracellular matrix was spontaneously and gradually detached when the grown cell sheet was removed from the incubator and exposed to room temperature (~30 °C within minutes.

  15. Methylcellulose based thermally reversible hydrogel system for tissue engineering applications.

    Science.gov (United States)

    Thirumala, Sreedhar; Gimble, Jeffrey M; Devireddy, Ram V

    2013-06-25

    The thermoresponsive behavior of a Methylcellulose (MC) polymer was systematically investigated to determine its usability in constructing MC based hydrogel systems in cell sheet engineering applications. Solution-gel analyses were made to study the effects of polymer concentration, molecular weight and dissolved salts on the gelation of three commercially available MCs using differential scanning calorimeter and rheology. For investigation of the hydrogel stability and fluid uptake capacity, swelling and degradation experiments were performed with the hydrogel system exposed to cell culture solutions at incubation temperature for several days. From these experiments, the optimal composition of MC-water-salt that was able to produce stable hydrogels at or above 32 °C, was found to be 12% to 16% of MC (Mol. wt. of 15,000) in water with 0.5× PBS (~150mOsm). This stable hydrogel system was then evaluated for a week for its efficacy to support the adhesion and growth of specific cells in culture; in our case the stromal/stem cells derived from human adipose tissue derived stem cells (ASCs). The results indicated that the addition (evenly spread) of ~200 µL of 2 mg/mL bovine collagen type -I (pH adjusted to 7.5) over the MC hydrogel surface at 37 °C is required to improve the ASC adhesion and proliferation. Upon confluence, a continuous monolayer ASC sheet was formed on the surface of the hydrogel system and an intact cell sheet with preserved cell-cell and cell-extracellular matrix was spontaneously and gradually detached when the grown cell sheet was removed from the incubator and exposed to room temperature (~30 °C) within minutes.

  16. Interactive scalable condensation of reverse engineered UML class diagrams for software comprehension

    NARCIS (Netherlands)

    Osman, Mohd Hafeez Bin

    2015-01-01

    Software design documentation is a valuable aid in software comprehension. However, keeping the software design up-to-date with evolving source code is challenging and time-consuming. Reverse engineering is one of the options for recovering software architecture from the implementation code.

  17. A reverse engineering algorithm for neural networks, applied to the subthalamopallidal network of basal ganglia.

    Science.gov (United States)

    Floares, Alexandru George

    2008-01-01

    Modeling neural networks with ordinary differential equations systems is a sensible approach, but also very difficult. This paper describes a new algorithm based on linear genetic programming which can be used to reverse engineer neural networks. The RODES algorithm automatically discovers the structure of the network, including neural connections, their signs and strengths, estimates its parameters, and can even be used to identify the biophysical mechanisms involved. The algorithm is tested on simulated time series data, generated using a realistic model of the subthalamopallidal network of basal ganglia. The resulting ODE system is highly accurate, and results are obtained in a matter of minutes. This is because the problem of reverse engineering a system of coupled differential equations is reduced to one of reverse engineering individual algebraic equations. The algorithm allows the incorporation of common domain knowledge to restrict the solution space. To our knowledge, this is the first time a realistic reverse engineering algorithm based on linear genetic programming has been applied to neural networks.

  18. The investment strategies of sovereign wealth funds: A reverse engineered pitch

    Directory of Open Access Journals (Sweden)

    Stanislav Martínek

    2017-12-01

    Full Text Available This letter describes personal reflection based on the utilization of the Faff’s (2017, Pitching Research pitch template for a reverse engineering technique in order to summarize, evaluate and properly interpret information from articles in respected scientific journals which represents key or seminal scientific research work upon which a researcher built his/her scientific work.

  19. Plasma engineering design of a compact reversed-field pinch reactor (CRFPR)

    International Nuclear Information System (INIS)

    Bathke, C.G.; Embrechts, M.J.; Hagenson, R.L.; Krakowski, R.A.; Miller, R.L.

    1983-01-01

    The rationale for and the characteristics of the high-power-density Compact Reversed-Field Pinch Reactor (CRFPR) are discussed. Particular emphasis is given to key plasma engineering aspects of the conceptual design, including plasma operations, current drive, and impurity/ash control by means of pumped limiters or magnetic divertors. A brief description of the Fusion-Power-Core integration is given

  20. Cell-free synthetic biology for in vitro prototype engineering.

    Science.gov (United States)

    Moore, Simon J; MacDonald, James T; Freemont, Paul S

    2017-06-15

    Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. © 2017 The Author(s).

  1. Geomagnetic polarity reversals as a mechanism for the punctuated equilibrium model of biological evolution

    International Nuclear Information System (INIS)

    Welsh, J.S.; Welsh, A.L.; Welsh, W.F.

    2003-01-01

    In contrast to what is predicted by classical Darwinian theory (phyletic gradualism), the fossil record typically displays a pattern of relatively sudden, dramatic changes as detailed by Eldregde and Gould's model of punctuated equilibrium. Evolutionary biologists have been at a loss to explain the ultimate source of the new mutations that drive evolution. One hypothesis holds that the abrupt speciation seen in the punctuated equilibrium model is secondary to an increased mutation rate resulting from periodically increased levels of ionizing radiation on the Earth's surface. Sporadic geomagnetic pole reversals, occurring every few million years on the average, are accompanied by alterations in the strength of the Earth's magnetic field and magnetosphere. This diminution may allow charged cosmic radiation to bombard Earth with less attenuation, thereby resulting in increased mutation rates. This episodic fluctuation in the magnetosphere is an attractive mechanism for the observed fossil record. Selected periods and epochs of geologic history for which data was available were reviewed for both geomagnetic pole reversal history and fossil record. Anomalies in either were scrutinized in greater depth and correlations were made. A 35 million year span (118-83 Ma) was identified during the Early/Middle Cretaceous period that was devoid of geomagnetic polarity reversals(the Cretaceous normal superchron). Examination of the fossil record (including several invertebrate and vertebrate taxons) during the Cretaceous normal superchron does not reveal any significant gap or slowing of speciation. Although increased terrestrial radiation exposure due to a diminution of the Earth's magnetosphere caused by a reversal of geomagnetic polarity is an attractive explanation for the mechanism of punctuated equilibrium, our investigation suggests that such polarity reversals cannot fully provide the driving force behind biological evolution. Further research is required to determine if

  2. Plant synthetic biology for molecular engineering of signalling and development.

    Science.gov (United States)

    Nemhauser, Jennifer L; Torii, Keiko U

    2016-03-02

    Molecular genetic studies of model plants in the past few decades have identified many key genes and pathways controlling development, metabolism and environmental responses. Recent technological and informatics advances have led to unprecedented volumes of data that may uncover underlying principles of plants as biological systems. The newly emerged discipline of synthetic biology and related molecular engineering approaches is built on this strong foundation. Today, plant regulatory pathways can be reconstituted in heterologous organisms to identify and manipulate parameters influencing signalling outputs. Moreover, regulatory circuits that include receptors, ligands, signal transduction components, epigenetic machinery and molecular motors can be engineered and introduced into plants to create novel traits in a predictive manner. Here, we provide a brief history of plant synthetic biology and significant recent examples of this approach, focusing on how knowledge generated by the reference plant Arabidopsis thaliana has contributed to the rapid rise of this new discipline, and discuss potential future directions.

  3. Reverse engineering a mouse embryonic stem cell-specific transcriptional network reveals a new modulator of neuronal differentiation.

    Science.gov (United States)

    De Cegli, Rossella; Iacobacci, Simona; Flore, Gemma; Gambardella, Gennaro; Mao, Lei; Cutillo, Luisa; Lauria, Mario; Klose, Joachim; Illingworth, Elizabeth; Banfi, Sandro; di Bernardo, Diego

    2013-01-01

    Gene expression profiles can be used to infer previously unknown transcriptional regulatory interaction among thousands of genes, via systems biology 'reverse engineering' approaches. We 'reverse engineered' an embryonic stem (ES)-specific transcriptional network from 171 gene expression profiles, measured in ES cells, to identify master regulators of gene expression ('hubs'). We discovered that E130012A19Rik (E13), highly expressed in mouse ES cells as compared with differentiated cells, was a central 'hub' of the network. We demonstrated that E13 is a protein-coding gene implicated in regulating the commitment towards the different neuronal subtypes and glia cells. The overexpression and knock-down of E13 in ES cell lines, undergoing differentiation into neurons and glia cells, caused a strong up-regulation of the glutamatergic neurons marker Vglut2 and a strong down-regulation of the GABAergic neurons marker GAD65 and of the radial glia marker Blbp. We confirmed E13 expression in the cerebral cortex of adult mice and during development. By immuno-based affinity purification, we characterized protein partners of E13, involved in the Polycomb complex. Our results suggest a role of E13 in regulating the division between glutamatergic projection neurons and GABAergic interneurons and glia cells possibly by epigenetic-mediated transcriptional regulation.

  4. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2014

    Energy Technology Data Exchange (ETDEWEB)

    Voigt, Christopher [Massachusetts Institute of Technology

    2014-07-01

    SEED2014 focused on advances in the science and technology emerging from the field of synthetic biology. We broadly define this as technologies that accelerate the process of genetic engineering. It highlighted new tool development, as well as the application of these tools to diverse problems in biotechnology, including therapeutics, industrial chemicals and fuels, natural products, and agriculture. Systems spanned from in vitro experiments and viruses, through diverse bacteria, to eukaryotes (yeast, mammalian cells, plants).

  5. Agent-based re-engineering of ErbB signaling: a modeling pipeline for integrative systems biology.

    Science.gov (United States)

    Das, Arya A; Ajayakumar Darsana, T; Jacob, Elizabeth

    2017-03-01

    Experiments in systems biology are generally supported by a computational model which quantitatively estimates the parameters of the system by finding the best fit to the experiment. Mathematical models have proved to be successful in reverse engineering the system. The data generated is interpreted to understand the dynamics of the underlying phenomena. The question we have sought to answer is that - is it possible to use an agent-based approach to re-engineer a biological process, making use of the available knowledge from experimental and modelling efforts? Can the bottom-up approach benefit from the top-down exercise so as to create an integrated modelling formalism for systems biology? We propose a modelling pipeline that learns from the data given by reverse engineering, and uses it for re-engineering the system, to carry out in-silico experiments. A mathematical model that quantitatively predicts co-expression of EGFR-HER2 receptors in activation and trafficking has been taken for this study. The pipeline architecture takes cues from the population model that gives the rates of biochemical reactions, to formulate knowledge-based rules for the particle model. Agent-based simulations using these rules, support the existing facts on EGFR-HER2 dynamics. We conclude that, re-engineering models, built using the results of reverse engineering, opens up the possibility of harnessing the power pack of data which now lies scattered in literature. Virtual experiments could then become more realistic when empowered with the findings of empirical cell biology and modelling studies. Implemented on the Agent Modelling Framework developed in-house. C ++ code templates available in Supplementary material . liz.csir@gmail.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  6. Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

    Science.gov (United States)

    Wen, Shameng; Meng, Qingkun; Feng, Chao; Tang, Chaojing

    2017-01-01

    Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

  7. Protocol vulnerability detection based on network traffic analysis and binary reverse engineering.

    Directory of Open Access Journals (Sweden)

    Shameng Wen

    Full Text Available Network protocol vulnerability detection plays an important role in many domains, including protocol security analysis, application security, and network intrusion detection. In this study, by analyzing the general fuzzing method of network protocols, we propose a novel approach that combines network traffic analysis with the binary reverse engineering method. For network traffic analysis, the block-based protocol description language is introduced to construct test scripts, while the binary reverse engineering method employs the genetic algorithm with a fitness function designed to focus on code coverage. This combination leads to a substantial improvement in fuzz testing for network protocols. We build a prototype system and use it to test several real-world network protocol implementations. The experimental results show that the proposed approach detects vulnerabilities more efficiently and effectively than general fuzzing methods such as SPIKE.

  8. Using a Formal Approach for Reverse Engineering and Design Recovery to Support Software Reuse

    Science.gov (United States)

    Gannod, Gerald C.

    2002-01-01

    This document describes 3rd year accomplishments and summarizes overall project accomplishments. Included as attachments are all published papers from year three. Note that the budget for this project was discontinued after year two, but that a residual budget from year two allowed minimal continuance into year three. Accomplishments include initial investigations into log-file based reverse engineering, service-based software reuse, and a source to XML generator.

  9. An Analytical Reverse Engineering of IELTS Listening Tasks for a Construct Model

    OpenAIRE

    Masood Khalili Sabet; Hamid Reza Babaee Bormanaki

    2017-01-01

    The study reported here was concerned with the issue of reverse engineering of language test items as it relates to the identification of the language constructs underlying listening tasks of LELTS test. In this regard, the IELTS examination papers, from IELTS 1 to IELTS 10 were compiled as a corpus for the analysis. Tasks were analyzed using a taxonomic frame work adopted from Moore, Morton and price (2012), that was originally adapted from Weir and Urquhart (1998), with a focus on two dimen...

  10. A Survey of Automatic Protocol Reverse Engineering Approaches, Methods, and Tools on the Inputs and Outputs View

    Directory of Open Access Journals (Sweden)

    Baraka D. Sija

    2018-01-01

    Full Text Available A network protocol defines rules that control communications between two or more machines on the Internet, whereas Automatic Protocol Reverse Engineering (APRE defines the way of extracting the structure of a network protocol without accessing its specifications. Enough knowledge on undocumented protocols is essential for security purposes, network policy implementation, and management of network resources. This paper reviews and analyzes a total of 39 approaches, methods, and tools towards Protocol Reverse Engineering (PRE and classifies them into four divisions, approaches that reverse engineer protocol finite state machines, protocol formats, and both protocol finite state machines and protocol formats to approaches that focus directly on neither reverse engineering protocol formats nor protocol finite state machines. The efficiency of all approaches’ outputs based on their selected inputs is analyzed in general along with appropriate reverse engineering inputs format. Additionally, we present discussion and extended classification in terms of automated to manual approaches, known and novel categories of reverse engineered protocols, and a literature of reverse engineered protocols in relation to the seven layers’ OSI (Open Systems Interconnection model.

  11. [Reconstruction and measurement of a digital dental model using grating projection and reverse engineering].

    Science.gov (United States)

    Zhenzhen, Wang; Yi, Lu; Jun, Song; Jun, Chen; Qin, Zhou

    2015-02-01

    This work lays the foundation for establishing a digital model database with normal occlusion. A digital dental cast is acquired through grating projection, and model features are measured through reverse engineering. The grating projection system controlled by a computer was projected onto the surface of a normal dental model. Three-dimensional contour data were obtained through multi-angle shooting. A three-dimensional model was constructed, and the model features were analyzed by using reverse engineering. The digital model was compared with the plaster model to determine the accuracy of the measurement system. The structure of three-dimensional reconstruction model was clear. The digital models of two measurements exhibited no significant difference (P > 0.05). When digital and plaster models were measured, we found that the crown length and arch width were not statistically different (P > 0.05), whereas the difference between the crown width and arch length was statistically significant (P model by using the grating projection technique and reverse engineering can be used for dental model measurement in clinic al and scientific research and can provide a scientific method for establishing a digital model database with normal occlusion.

  12. A novel technique for presurgical nasoalveolar molding using computer-aided reverse engineering and rapid prototyping.

    Science.gov (United States)

    Yu, Quan; Gong, Xin; Wang, Guo-Min; Yu, Zhe-Yuan; Qian, Yu-Fen; Shen, Gang

    2011-01-01

    To establish a new method of presurgical nasoalveolar molding (NAM) using computer-aided reverse engineering and rapid prototyping technique in infants with unilateral cleft lip and palate (UCLP). Five infants (2 males and 3 females with mean age of 1.2 w) with complete UCLP were recruited. All patients were subjected to NAM before the cleft lip repair. The upper denture casts were recorded using a three-dimensional laser scanner within 2 weeks after birth in UCLP infants. A digital model was constructed and analyzed to simulate the NAM procedure with reverse engineering software. The digital geometrical data were exported to print the solid model with rapid prototyping system. The whole set of appliances was fabricated based on these solid models. Laser scanning and digital model construction simplified the NAM procedure and estimated the treatment objective. The appliances were fabricated based on the rapid prototyping technique, and for each patient, the complete set of appliances could be obtained at one time. By the end of presurgical NAM treatment, the cleft was narrowed, and the malformation of nasoalveolar segments was aligned normally. We have developed a novel technique of presurgical NAM based on a computer-aided design. The accurate digital denture model of UCLP infants could be obtained with laser scanning. The treatment design and appliance fabrication could be simplified with a computer-aided reverse engineering and rapid prototyping technique.

  13. CellNet: network biology applied to stem cell engineering.

    Science.gov (United States)

    Cahan, Patrick; Li, Hu; Morris, Samantha A; Lummertz da Rocha, Edroaldo; Daley, George Q; Collins, James J

    2014-08-14

    Somatic cell reprogramming, directed differentiation of pluripotent stem cells, and direct conversions between differentiated cell lineages represent powerful approaches to engineer cells for research and regenerative medicine. We have developed CellNet, a network biology platform that more accurately assesses the fidelity of cellular engineering than existing methodologies and generates hypotheses for improving cell derivations. Analyzing expression data from 56 published reports, we found that cells derived via directed differentiation more closely resemble their in vivo counterparts than products of direct conversion, as reflected by the establishment of target cell-type gene regulatory networks (GRNs). Furthermore, we discovered that directly converted cells fail to adequately silence expression programs of the starting population and that the establishment of unintended GRNs is common to virtually every cellular engineering paradigm. CellNet provides a platform for quantifying how closely engineered cell populations resemble their target cell type and a rational strategy to guide enhanced cellular engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. From biology to mathematical models and back: teaching modeling to biology students, and biology to math and engineering students.

    Science.gov (United States)

    Chiel, Hillel J; McManus, Jeffrey M; Shaw, Kendrick M

    2010-01-01

    We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a "live" textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology.

  15. From Biology to Mathematical Models and Back: Teaching Modeling to Biology Students, and Biology to Math and Engineering Students

    Science.gov (United States)

    McManus, Jeffrey M.; Shaw, Kendrick M.

    2010-01-01

    We describe the development of a course to teach modeling and mathematical analysis skills to students of biology and to teach biology to students with strong backgrounds in mathematics, physics, or engineering. The two groups of students have different ways of learning material and often have strong negative feelings toward the area of knowledge that they find difficult. To give students a sense of mastery in each area, several complementary approaches are used in the course: 1) a “live” textbook that allows students to explore models and mathematical processes interactively; 2) benchmark problems providing key skills on which students make continuous progress; 3) assignment of students to teams of two throughout the semester; 4) regular one-on-one interactions with instructors throughout the semester; and 5) a term project in which students reconstruct, analyze, extend, and then write in detail about a recently published biological model. Based on student evaluations and comments, an attitude survey, and the quality of the students' term papers, the course has significantly increased the ability and willingness of biology students to use mathematical concepts and modeling tools to understand biological systems, and it has significantly enhanced engineering students' appreciation of biology. PMID:20810957

  16. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering.

    Science.gov (United States)

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-04-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways. © 2016 The Author(s).

  17. SYSTEMS BIOLOGY AND METABOLIC ENGINEERING OF ARTHROSPIRA CELL FACTORIES

    Directory of Open Access Journals (Sweden)

    Amornpan Klanchui

    2012-10-01

    Full Text Available Arthrospira are attractive candidates to serve as cell factories for production of many valuable compounds useful for food, feed, fuel and pharmaceutical industries. In connection with the development of sustainable bioprocessing, it is a challenge to design and develop efficient Arthrospira cell factories which can certify effective conversion from the raw materials (i.e. CO2 and sun light into desired products. With the current availability of the genome sequences and metabolic models of Arthrospira, the development of Arthrospira factories can now be accelerated by means of systems biology and the metabolic engineering approach. Here, we review recent research involving the use of Arthrospira cell factories for industrial applications, as well as the exploitation of systems biology and the metabolic engineering approach for studying Arthrospira. The current status of genomics and proteomics through the development of the genome-scale metabolic model of Arthrospira, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies are discussed. At the end, the perspective and future direction on Arthrospira cell factories for industrial biotechnology are presented.

  18. Engineering Therapeutic T Cells: From Synthetic Biology to Clinical Trials.

    Science.gov (United States)

    Esensten, Jonathan H; Bluestone, Jeffrey A; Lim, Wendell A

    2017-01-24

    Engineered T cells are currently in clinical trials to treat patients with cancer, solid organ transplants, and autoimmune diseases. However, the field is still in its infancy. The design, and manufacturing, of T cell therapies is not standardized and is performed mostly in academic settings by competing groups. Reliable methods to define dose and pharmacokinetics of T cell therapies need to be developed. As of mid-2016, there are no US Food and Drug Administration (FDA)-approved T cell therapeutics on the market, and FDA regulations are only slowly adapting to the new technologies. Further development of engineered T cell therapies requires advances in immunology, synthetic biology, manufacturing processes, and government regulation. In this review, we outline some of these challenges and discuss the contributions that pathologists can make to this emerging field.

  19. Insights gained from the reverse engineering of gene networks in keloid fibroblasts

    Directory of Open Access Journals (Sweden)

    Phan Toan

    2011-05-01

    Full Text Available Abstract Background Keloids are protrusive claw-like scars that have a propensity to recur even after surgery, and its molecular etiology remains elusive. The goal of reverse engineering is to infer gene networks from observational data, thus providing insight into the inner workings of a cell. However, most attempts at modeling biological networks have been done using simulated data. This study aims to highlight some of the issues involved in working with experimental data, and at the same time gain some insights into the transcriptional regulatory mechanism present in keloid fibroblasts. Methods Microarray data from our previous study was combined with microarray data obtained from the literature as well as new microarray data generated by our group. For the physical approach, we used the fREDUCE algorithm for correlating expression values to binding motifs. For the influence approach, we compared the Bayesian algorithm BANJO with the information theoretic method ARACNE in terms of performance in recovering known influence networks obtained from the KEGG database. In addition, we also compared the performance of different normalization methods as well as different types of gene networks. Results Using the physical approach, we found consensus sequences that were active in the keloid condition, as well as some sequences that were responsive to steroids, a commonly used treatment for keloids. From the influence approach, we found that BANJO was better at recovering the gene networks compared to ARACNE and that transcriptional networks were better suited for network recovery compared to cytokine-receptor interaction networks and intracellular signaling networks. We also found that the NFKB transcriptional network that was inferred from normal fibroblast data was more accurate compared to that inferred from keloid data, suggesting a more robust network in the keloid condition. Conclusions Consensus sequences that were found from this study are

  20. Is nanotechnology the key to unravel and engineer biological processes?

    Science.gov (United States)

    Navarro, Melba; Planell, Josep A

    2012-01-01

    Regenerative medicine is an emerging field aiming to the development of new reparative strategies to treat degenerative diseases, injury, and trauma through developmental pathways in order to rebuild the architecture of the original injured organ and take over its functionality. Most of the processes and interactions involved in the regenerative process take place at subcellular scale. Nanotechnology provides the tools and technology not only to detect, to measure, or to image the interactions between the different biomolecules and biological entities, but also to control and guide the regenerative process. The relevance of nanotechnology for the development of regenerative medicine as well as an overview of the different tools that contribute to unravel and engineer biological systems are presented in this chapter. In addition, general data about the social impact and global investment in nanotechnology are provided.

  1. Simple glycolipids of microbes: Chemistry, biological activity and metabolic engineering

    Directory of Open Access Journals (Sweden)

    Ahmad Mohammad Abdel-Mawgoud

    2018-03-01

    Full Text Available Glycosylated lipids (GLs are added-value lipid derivatives of great potential. Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents, they have diverse biological activities with promising biomedical and cosmeceutical applications. Glycolipids, especially those of microbial origin, have interesting antimicrobial, anticancer, antiparasitic as well as immunomodulatory activities. Nonetheless, GLs are hardly accessing the market because of their high cost of production. We believe that experience of metabolic engineering (ME of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications. This review presents chemical groups of bacterial and fungal GLs, their biological activities, their general biosynthetic pathways and an insight on ME strategies for their production.

  2. PREFACE: Nanobiology: from physics and engineering to biology

    Science.gov (United States)

    Nussinov, Ruth; Alemán, Carlos

    2006-03-01

    Biological systems are inherently nano in scale. Unlike nanotechnology, nanobiology is characterized by the interplay between physics, materials science, synthetic organic chemistry, engineering and biology. Nanobiology is a new discipline, with the potential of revolutionizing medicine: it combines the tools, ideas and materials of nanoscience and biology; it addresses biological problems that can be studied and solved by nanotechnology; it devises ways to construct molecular devices using biomacromolecules; and it attempts to build molecular machines utilizing concepts seen in nature. Its ultimate aim is to be able to predictably manipulate these, tailoring them to specified needs. Nanobiology targets biological systems and uses biomacromolecules. Hence, on the one hand, nanobiology is seemingly constrained in its scope as compared to general nanotechnology. Yet the amazing intricacy of biological systems, their complexity, and the richness of the shapes and properties provided by the biological polymers, enrich nanobiology. Targeting biological systems entails comprehension of how they work and the ability to use their components in design. From the physical standpoint, ultimately, if we are to understand biology we need to learn how to apply physical principles to figure out how these systems actually work. The goal of nanobiology is to assist in probing these systems at the appropriate length scale, heralding a new era in the biological, physical and chemical sciences. Biology is increasingly asking quantitative questions. Quantitation is essential if we are to understand how the cell works, and the details of its regulation. The physical sciences provide tools and strategies to obtain accurate measurements and simulate the information to allow comprehension of the processes. Nanobiology is at the interface of the physical and the biological sciences. Biology offers to the physical sciences fascinating problems, sophisticated systems and a rich repertoire of

  3. Analysis and simulation on two types of thrust reversers in an aircraft engine

    Directory of Open Access Journals (Sweden)

    Tian Feng

    2017-01-01

    Full Text Available With rapid development of new composite material and manufacturing, innovative engineering solutions are supplied to the advanced nacelle, such as integrated propulsion system(IPS, carbon-fiber composite inner skin by single-piece molding process,which offers a reduction in fuel burn and less noise produced by engines. The advanced nacelle has an O-duct thrust reverser demonstrator whose composite structure is in the form of an “O” as opposed to the traditional “D-duct”. A comparative study is to be conducted to investigate the differences between the latest O-duct and conventional D-duct in numerical approaches. To focus on the quantitative analysis of thrust reverser’s operation, this paper mainly uses CATIA/Digital Mock Up(DMU to simulate under deployment and stowed conditions of two different thrust reverser. After comparing the structural weight, the design models of blocker door are built for kinematic analysis of relevant mechanism and simulation. The results show that simplified design and elimination of multiple interfaces generates weight saving, O-duct improves airflows within the engine, meanwhile D-duct has excellent cost effective and maintainability.

  4. Reverse engineering of a railcar prototype via energetic macroscopic representation approach

    International Nuclear Information System (INIS)

    Agbli, Kréhi Serge; Hissel, Daniel; Sorrentino, Marco; Chauvet, Frédéric; Pouget, Julien

    2016-01-01

    Highlights: • A complex EMR model of a new railcar range has been developed. • A satisfactory assessment of the fuel consumption of the railcar. • The significant potential benefits are attainable by hybridizing the original railcar. • The regenerative braking can provide up to 240 kW h saving. - Abstract: Energetic Macroscopic Representation (EMR) modelling approach is proposed to perform model-based reverse-engineering of a new railcar range, having six propulsion units, each consisting of a diesel engine and a traction motor. Particularly, EMR intrinsic features were exploited to perform phenomenological structuration of power flows, thus allowing proper and comprehensive modelling of complex systems, such as the under-study railcar. Based on some prospective real trips, selected in such a way as to enable realistic evaluation of effective railcar effort, EMR-based prediction of railcar energy consumption is performed. Furthermore, physical consistency of each powertrain component operation was carefully verified. The suitability of EMR approach was thus proven effective to perform reverse-engineering of known specifications and available experimental data, with the final aim of reconstructing a high fidelity computational tool that meets computational burden requirements for subsequent model-based tasks deployment. Finally, specific simulation analyses were performed to evaluate the potential benefits attainable through electric hybridization of the original powertrain.

  5. Reversing flow catalytic converter for a natural gas/diesel dual fuel engine

    Energy Technology Data Exchange (ETDEWEB)

    Liu, E.; Checkel, M.D. [Alberta Univ., Edmonton, AB (Canada). Dept. of Mechanical Engineering; Hayes, R.E. [Alberta Univ., Edmonton, AB (Canada). Dept. of Chemical and Materials Engineering; Alberta Univ., Edmonton, AB (Canada). Dept. of Mechanical Engineering; Zheng, M.; Mirosh, E. [Alternative Fuel Systems Inc., Calgary, AB (Canada)

    2001-07-01

    An experimental and modelling study was performed for a reverse flow catalytic converter attached to a natural gas/diesel dual fuel engine. The catalytic converter had a segmented ceramic monolith honeycomb substrate and a catalytic washcoat containing a predominantly palladium catalyst. A one-dimensional single channel model was used to simulate the operation of the converter. The kinetics of the CO and methane oxidation followed first-order behaviour. The activation energy for the oxidation of methane showed a change with temperature, dropping from a value of 129 to 35 kJ/mol at a temperature of 874 K. The reverse flow converter was able to achieve high reactor temperature under conditions of low inlet gas temperature, provided that the initial reactor temperature was sufficiently high. (author)

  6. Multiplexed genome engineering and genotyping methods applications for synthetic biology and metabolic engineering.

    Science.gov (United States)

    Wang, Harris H; Church, George M

    2011-01-01

    Engineering at the scale of whole genomes requires fundamentally new molecular biology tools. Recent advances in recombineering using synthetic oligonucleotides enable the rapid generation of mutants at high efficiency and specificity and can be implemented at the genome scale. With these techniques, libraries of mutants can be generated, from which individuals with functionally useful phenotypes can be isolated. Furthermore, populations of cells can be evolved in situ by directed evolution using complex pools of oligonucleotides. Here, we discuss ways to utilize these multiplexed genome engineering methods, with special emphasis on experimental design and implementation. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. A reverse engineering methodology for nickel alloy turbine blades with internal features

    DEFF Research Database (Denmark)

    Gameros, A.; De Chiffre, Leonardo; Siller, H.R.

    2015-01-01

    The scope of this work is to present a reverse engineering (RE) methodology for freeform surfaces, based on a case study of a turbine blade made of Inconel, including the reconstruction of its internal cooling system. The methodology uses an optical scanner and X-ray computed tomography (CT......) equipment. Traceability of the measurements was obtained through the use of a Modular Freeform Gage (MFG). An uncertainty budget is presented for both measuring technologies and results show that the RE methodology presented is promising when comparing uncertainty values against common industrial tolerances....

  8. PGASO: A synthetic biology tool for engineering a cellulolytic yeast

    Directory of Open Access Journals (Sweden)

    Chang Jui-Jen

    2012-07-01

    Full Text Available Abstract Background To achieve an economical cellulosic ethanol production, a host that can do both cellulosic saccharification and ethanol fermentation is desirable. However, to engineer a non-cellulolytic yeast to be such a host requires synthetic biology techniques to transform multiple enzyme genes into its genome. Results A technique, named Promoter-based Gene Assembly and Simultaneous Overexpression (PGASO, that employs overlapping oligonucleotides for recombinatorial assembly of gene cassettes with individual promoters, was developed. PGASO was applied to engineer Kluyveromycesmarxianus KY3, which is a thermo- and toxin-tolerant yeast. We obtained a recombinant strain, called KR5, that is capable of simultaneously expressing exoglucanase and endoglucanase (both of Trichodermareesei, a beta-glucosidase (from a cow rumen fungus, a neomycin phosphotransferase, and a green fluorescent protein. High transformation efficiency and accuracy were achieved as ~63% of the transformants was confirmed to be correct. KR5 can utilize beta-glycan, cellobiose or CMC as the sole carbon source for growth and can directly convert cellobiose and beta-glycan to ethanol. Conclusions This study provides the first example of multi-gene assembly in a single step in a yeast species other than Saccharomyces cerevisiae. We successfully engineered a yeast host with a five-gene cassette assembly and the new host is capable of co-expressing three types of cellulase genes. Our study shows that PGASO is an efficient tool for simultaneous expression of multiple enzymes in the kefir yeast KY3 and that KY3 can serve as a host for developing synthetic biology tools.

  9. An analysis of extended entity relationship constructs extraction in database reverse engineering approaches

    International Nuclear Information System (INIS)

    Jilani, M.A.; Aziz, A.; Hussain, T.

    2008-01-01

    Database reverse Engineering is technique used for transforming relational schema into a conceptual schema for finding and fixing design flaw for maintaining and re-engineering database systems for the integration of database system with another and migration of a database system from one platform to another. We studied the approaches from year 1993 to 2006 to find out which EER construct cannot be retrieved by most of the DBRE approaches so that they can be retrieved in the future. For each EER construct that can be retrieved by using a given DBRE approach. We show whether they are retrieved without user involvement (automatically). Partial user involvement (semi-automatically) or full user involvement (manually). We also discuss the relevant advantages and limitations of each DBRE technique considered in this paper. (author)

  10. Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

    Science.gov (United States)

    Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

    2012-01-01

    Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

  11. A model of engineering materials inspired by biological tissues

    Directory of Open Access Journals (Sweden)

    Holeček M.

    2009-12-01

    Full Text Available The perfect ability of living tissues to control and adapt their mechanical properties to varying external conditions may be an inspiration for designing engineering materials. An interesting example is the smooth muscle tissue since this "material" is able to change its global mechanical properties considerably by a subtle mechanism within individual muscle cells. Multi-scale continuum models may be useful in designing essentially simpler engineering materials having similar properties. As an illustration we present the model of an incompressible material whose microscopic structure is formed by flexible, soft but incompressible balls connected mutually by linear springs. This simple model, however, shows a nontrivial nonlinear behavior caused by the incompressibility of balls and is very sensitive on some microscopic parameters. It may elucidate the way by which "small" changes in biopolymer networks within individual muscular cells may control the stiffness of the biological tissue, which outlines a way of designing similar engineering materials. The 'balls and springs' material presents also prestress-induced stiffening and allows elucidating a contribution of extracellular fluids into the tissue’s viscous properties.

  12. An Evaluation of Active Learning Causal Discovery Methods for Reverse-Engineering Local Causal Pathways of Gene Regulation

    Science.gov (United States)

    Ma, Sisi; Kemmeren, Patrick; Aliferis, Constantin F.; Statnikov, Alexander

    2016-01-01

    Reverse-engineering of causal pathways that implicate diseases and vital cellular functions is a fundamental problem in biomedicine. Discovery of the local causal pathway of a target variable (that consists of its direct causes and direct effects) is essential for effective intervention and can facilitate accurate diagnosis and prognosis. Recent research has provided several active learning methods that can leverage passively observed high-throughput data to draft causal pathways and then refine the inferred relations with a limited number of experiments. The current study provides a comprehensive evaluation of the performance of active learning methods for local causal pathway discovery in real biological data. Specifically, 54 active learning methods/variants from 3 families of algorithms were applied for local causal pathways reconstruction of gene regulation for 5 transcription factors in S. cerevisiae. Four aspects of the methods’ performance were assessed, including adjacency discovery quality, edge orientation accuracy, complete pathway discovery quality, and experimental cost. The results of this study show that some methods provide significant performance benefits over others and therefore should be routinely used for local causal pathway discovery tasks. This study also demonstrates the feasibility of local causal pathway reconstruction in real biological systems with significant quality and low experimental cost. PMID:26939894

  13. Future of Chemical Engineering: Integrating Biology into the Undergraduate ChE Curriculum

    Science.gov (United States)

    Mosto, Patricia; Savelski, Mariano; Farrell, Stephanie H.; Hecht, Gregory B.

    2007-01-01

    Integrating biology in the chemical engineering curriculum seems to be the future for chemical engineering programs nation and worldwide. Rowan University's efforts to address this need include a unique chemical engineering curriculum with an intensive biology component integrated throughout from freshman to senior years. Freshman and Sophomore…

  14. Experiential Engineering through iGEM--An Undergraduate Summer Competition in Synthetic Biology

    Science.gov (United States)

    Mitchell, Rudolph; Dori, Yehudit Judy; Kuldell, Natalie H.

    2011-01-01

    Unlike students in other engineering disciplines, undergraduates in biological engineering typically have limited opportunity to develop design competencies, and even fewer chances to implement their designed projects. The international Genetically Engineered Machines (iGEM) competition is a student Synthetic Biology competition that, in 2009,…

  15. The development of a program analysis environment for Ada: Reverse engineering tools for Ada

    Science.gov (United States)

    Cross, James H., II

    1991-01-01

    The Graphical Representations of Algorithms, Structures, and Processes for Ada (GRASP/Ada) has successfully created and prototyped a new algorithm level graphical representation for Ada software, the Control Structure Diagram (CSD). The primary impetus for creation of the CSD was to improve the comprehension efficiency of Ada software and thus improve reliability and reduce costs. The emphasis was on the automatic generation of the CSD from Ada source code to support reverse engineering and maintenance. The CSD has the potential to replace traditional prettyprinted Ada source code. In Phase 1 of the GRASP/Ada project, the CSD graphical constructs were created and applied manually to several small Ada programs. A prototype (Version 1) was designed and implemented using FLEX and BISON running under the Virtual Memory System (VMS) on a VAX 11-780. In Phase 2, the prototype was improved and ported to the Sun 4 platform under UNIX. A user interface was designed and partially implemented. The prototype was applied successfully to numerous Ada programs ranging in size from several hundred to several thousand lines of source code. In Phase 3 of the project, the prototype was prepared for limited distribution (GRASP/Ada Version 3.0) to facilitate evaluation. The user interface was extensively reworked. The current prototype provides the capability for the user to generate CSD from Ada source code in a reverse engineering mode with a level of flexibility suitable for practical application.

  16. An Application of Reverse Engineering in Design of the Spur Gear

    Directory of Open Access Journals (Sweden)

    Adem Çiçek

    2010-06-01

    Full Text Available In this study, it is aimed that the gear parameters required the design of a spur gear are obtained by use of reverse engineering techniques. Therefore, point cloud of tooth profile of the manufactured spur gear is extracted by a coordinate measuring machine (CMM. The gear parameters are derived by processing the obtained point cloud. 3D model of the spur gear are modeled through this parameters in a CAD environment. In the system, a hybrid programming approach is used. Generating and processing the point cloud, extraction of the gear parameters are performed by Visual BASIC programming language. 3D modeling in the CAD environment is performed also by AutoLISP programming language due to programming simplicity. These two softwares are provided to be in harmony by integrating them. In the study, SolidworksTM and AutoCADTM are selected as CAD environments. With this study, an alternative approach for the design of the spur gear is presented and modeling of the gears in the CAD environment is carried out using reverse engineering techniques.

  17. Topology reconstruction for B-Rep modeling from 3D mesh in reverse engineering applications

    Science.gov (United States)

    Bénière, Roseline; Subsol, Gérard; Gesquière, Gilles; Le Breton, François; Puech, William

    2012-03-01

    Nowadays, most of the manufactured objects are designed using CAD (Computer-Aided Design) software. Nevertheless, for visualization, data exchange or manufacturing applications, the geometric model has to be discretized into a 3D mesh composed of a finite number of vertices and edges. But, in some cases, the initial model may be lost or unavailable. In other cases, the 3D discrete representation may be modified, for example after a numerical simulation, and does not correspond anymore to the initial model. A reverse engineering method is then required to reconstruct a 3D continuous representation from the discrete one. In previous work, we have presented a new approach for 3D geometric primitive extraction. In this paper, to complete our automatic and comprehensive reverse engineering process, we propose a method to construct the topology of the retrieved object. To reconstruct a B-Rep model, a new formalism is now introduced to define the adjacency relations. Then a new process is used to construct the boundaries of the object. The whole process is tested on 3D industrial meshes and bring a solution to recover B-Rep models.

  18. 1st Global Conference on Biomedical Engineering & 9th Asian-Pacific Conference on Medical and Biological Engineering

    CERN Document Server

    Wang, Shyh-Hau; Yeh, Ming-Long

    2015-01-01

    This volume presents the proceedings of the 9th Asian-Pacific Conference on Medical and Biological Engineering (APCMBE 2014). The proceedings address a broad spectrum of topics from Bioengineering and Biomedicine, like Biomaterials, Artificial Organs, Tissue Engineering, Nanobiotechnology and Nanomedicine, Biomedical Imaging, Bio MEMS, Biosignal Processing, Digital Medicine, BME Education. It helps medical and biological engineering professionals to interact and exchange their ideas and experiences.

  19. Experimental and modelling study of reverse flow catalytic converters for natural gas/diesel dual fuel engine pollution control

    Energy Technology Data Exchange (ETDEWEB)

    Liu, B.

    2000-07-01

    There is renewed interest in the development of natural gas vehicles in response to the challenge to reduce urban air pollution and consumption of petroleum. The natural gas/diesel dual fuel engine is one way to apply natural gas to the conventional diesel engine. Dual fuel engines operating on natural gas and diesel emit less nitrogen oxides, and less carbon soot to the air compared to conventional diesel engines. The problem is that at light loads, fuel efficiency is reduced and emissions of hydrocarbons and carbon monoxide are increased. This thesis focused on control methods for emissions of hydrocarbons and carbon monoxide in the dual fuel engine at light loads. This was done by developing a reverse flow catalytic converter to complement dual fuel engine exhaust characteristics. Experimental measurements and numerical simulations of reverse flow catalytic converters were conducted. Reverse flow creates a high reactor temperature even when the engine is run at low exhaust temperature levels at light loads. The increase in reactor temperature from reverse flow could be 2 or 3 times higher than the adiabatic temperature increase, which is based on the reactor inlet temperature and concentration. This temperature makes it possible for greater than 90 per cent of the hydrocarbon and carbon monoxide to be converted with a palladium based catalyst. Reverse flow appears to be better than conventional unidirectional flow to deal with natural gas/diesel dual fuel engine pollution at light loads. Reverse flow could also maintain reactor temperature at over 800 K and hydrocarbon conversion at about 80 per cent during testing. The newly presented model simulates reactor performance with reasonable accuracy. Both carbon monoxide and methane oxidation over the palladium catalyst in excess oxygen and water were described using first order kinetics.

  20. Synthetic biology approaches to engineering the nitrogen symbiosis in cereals.

    Science.gov (United States)

    Rogers, Christian; Oldroyd, Giles E D

    2014-05-01

    Nitrogen is abundant in the earth's atmosphere but, unlike carbon, cannot be directly assimilated by plants. The limitation this places on plant productivity has been circumvented in contemporary agriculture through the production and application of chemical fertilizers. The chemical reduction of nitrogen for this purpose consumes large amounts of energy and the reactive nitrogen released into the environment as a result of fertilizer application leads to greenhouse gas emissions, as well as widespread eutrophication of aquatic ecosystems. The environmental impacts are intensified by injudicious use of fertilizers in many parts of the world. Simultaneously, limitations in the production and supply of chemical fertilizers in other regions are leading to low agricultural productivity and malnutrition. Nitrogen can be directly fixed from the atmosphere by some bacteria and Archaea, which possess the enzyme nitrogenase. Some plant species, most notably legumes, have evolved close symbiotic associations with nitrogen-fixing bacteria. Engineering cereal crops with the capability to fix their own nitrogen could one day address the problems created by the over- and under-use of nitrogen fertilizers in agriculture. This could be achieved either by expression of a functional nitrogenase enzyme in the cells of the cereal crop or through transferring the capability to form a symbiotic association with nitrogen-fixing bacteria. While potentially transformative, these biotechnological approaches are challenging; however, with recent advances in synthetic biology they are viable long-term goals. This review discusses the possibility of these biotechnological solutions to the nitrogen problem, focusing on engineering the nitrogen symbiosis in cereals.

  1. Bacterial genome engineering and synthetic biology: combating pathogens.

    Science.gov (United States)

    Krishnamurthy, Malathy; Moore, Richard T; Rajamani, Sathish; Panchal, Rekha G

    2016-11-04

    The emergence and prevalence of multidrug resistant (MDR) pathogenic bacteria poses a serious threat to human and animal health globally. Nosocomial infections and common ailments such as pneumonia, wound, urinary tract, and bloodstream infections are becoming more challenging to treat due to the rapid spread of MDR pathogenic bacteria. According to recent reports by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC), there is an unprecedented increase in the occurrence of MDR infections worldwide. The rise in these infections has generated an economic strain worldwide, prompting the WHO to endorse a global action plan to improve awareness and understanding of antimicrobial resistance. This health crisis necessitates an immediate action to target the underlying mechanisms of drug resistance in bacteria. The advent of new bacterial genome engineering and synthetic biology (SB) tools is providing promising diagnostic and treatment plans to monitor and treat widespread recalcitrant bacterial infections. Key advances in genetic engineering approaches can successfully aid in targeting and editing pathogenic bacterial genomes for understanding and mitigating drug resistance mechanisms. In this review, we discuss the application of specific genome engineering and SB methods such as recombineering, clustered regularly interspaced short palindromic repeats (CRISPR), and bacterial cell-cell signaling mechanisms for pathogen targeting. The utility of these tools in developing antibacterial strategies such as novel antibiotic production, phage therapy, diagnostics and vaccine production to name a few, are also highlighted. The prevalent use of antibiotics and the spread of MDR bacteria raise the prospect of a post-antibiotic era, which underscores the need for developing novel therapeutics to target MDR pathogens. The development of enabling SB technologies offers promising solutions to deliver safe and effective antibacterial therapies.

  2. The bioartificial pancreas (BAP): Biological, chemical and engineering challenges.

    Science.gov (United States)

    Iacovacci, Veronica; Ricotti, Leonardo; Menciassi, Arianna; Dario, Paolo

    2016-01-15

    The bioartificial pancreas (BAP) represents a viable solution for the treatment of type 1 diabetes (T1D). By encapsulating pancreatic cells in a semipermeable membrane to allow nutrient, insulin and glucose exchange, the side effects produced by islets and whole organ transplantation-related immunosuppressive therapy can be circumvented. Several factors, mainly related to materials properties, capsule morphology and biological environment, play a key role in optimizing BAP systems. The BAP is an extremely complex delivery system for insulin. Despite considerable efforts, in some instances meeting with limited degree of success, a BAP capable of restoring physiological pancreas functions without the need for immunosuppressive drugs and of controlling blood glucose levels especially in large animal models and a few clinical trials, does not exist. The state of the art in terms of materials, fabrication techniques and cell sources, as well as the current status of commercial devices and clinical trials, are described in this overview from an interdisciplinary viewpoint. In addition, challenges to the creation of effective BAP systems are highlighted including future perspectives in terms of component integration from both a biological and an engineering viewpoint. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Proceedings of the European medical and biological engineering conference EMBEC '99 (Part I)

    International Nuclear Information System (INIS)

    Rehak, P.; Hutten, H.

    1999-01-01

    The proceedings books of the EMBEC '99 - European Medical and Biological Engineering Conference - are published in two parts as supplement 2 to the volume 37 of 'Medical and Biological Engineering and Computing', the official journal of the International Federation for Medical and Biological Engineering. More then 800 papers have been arranged in the order of the main topics and the topics of the special sessions of the conference. The paper of INIS relevance were worked up for INIS data bank. (author)

  4. Engineering a palette of eukaryotic chromoproteins for bacterial synthetic biology.

    Science.gov (United States)

    Liljeruhm, Josefine; Funk, Saskia K; Tietscher, Sandra; Edlund, Anders D; Jamal, Sabri; Wistrand-Yuen, Pikkei; Dyrhage, Karl; Gynnå, Arvid; Ivermark, Katarina; Lövgren, Jessica; Törnblom, Viktor; Virtanen, Anders; Lundin, Erik R; Wistrand-Yuen, Erik; Forster, Anthony C

    2018-01-01

    Coral reefs are colored by eukaryotic chromoproteins (CPs) that are homologous to green fluorescent protein. CPs differ from fluorescent proteins (FPs) by intensely absorbing visible light to give strong colors in ambient light. This endows CPs with certain advantages over FPs, such as instrument-free detection uncomplicated by ultra-violet light damage or background fluorescence, efficient Förster resonance energy transfer (FRET) quenching, and photoacoustic imaging. Thus, CPs have found utility as genetic markers and in teaching, and are attractive for potential cell biosensor applications in the field. Most near-term applications of CPs require expression in a different domain of life: bacteria. However, it is unclear which of the eukaryotic CP genes might be suitable and how best to assay them. Here, taking advantage of codon optimization programs in 12 cases, we engineered 14 CP sequences (meffRed, eforRed, asPink, spisPink, scOrange, fwYellow, amilGFP, amajLime, cjBlue, meffBlue, aeBlue, amilCP, tsPurple and gfasPurple) into a palette of Escherichia coli BioBrick plasmids. BioBricks comply with synthetic biology's most widely used, simplified, cloning standard. Differences in color intensities, maturation times and fitness costs of expression were compared under the same conditions, and visible readout of gene expression was quantitated. A surprisingly large variation in cellular fitness costs was found, resulting in loss of color in some overnight liquid cultures of certain high-copy-plasmid-borne CPs, and cautioning the use of multiple CPs as markers in competition assays. We solved these two problems by integrating pairs of these genes into the chromosome and by engineering versions of the same CP with very different colors. Availability of 14 engineered CP genes compared in E. coli , together with chromosomal mutants suitable for competition assays, should simplify and expand CP study and applications. There was no single plasmid-borne CP that combined

  5. [Computer aided design for fixed partial denture framework based on reverse engineering technology].

    Science.gov (United States)

    Sun, Yu-chun; Lü, Pei-jun; Wang, Yong

    2006-03-01

    To explore a computer aided design (CAD) route for the framework of domestic fixed partial denture (FPD) and confirm the suitable method of 3-D CAD. The working area of a dentition model was scanned with a 3-D mechanical scanner. Using the reverse engineering (RE) software, margin and border curves were extracted and several reference curves were created to ensure the dimension and location of pontic framework that was taken from the standard database. The shoulder parts of the retainers were created after axial surfaces constructed. The connecting areas, axial line and curving surface of the framework connector were finally created. The framework of a three-unit FPD was designed with RE technology, which showed smooth surfaces and continuous contours. The design route is practical. The result of this study is significant in theory and practice, which will provide a reference for establishing the computer aided design/computer aided manufacture (CAD/CAM) system of domestic FPD.

  6. Political science. Reverse-engineering censorship in China: randomized experimentation and participant observation.

    Science.gov (United States)

    King, Gary; Pan, Jennifer; Roberts, Margaret E

    2014-08-22

    Existing research on the extensive Chinese censorship organization uses observational methods with well-known limitations. We conducted the first large-scale experimental study of censorship by creating accounts on numerous social media sites, randomly submitting different texts, and observing from a worldwide network of computers which texts were censored and which were not. We also supplemented interviews with confidential sources by creating our own social media site, contracting with Chinese firms to install the same censoring technologies as existing sites, and--with their software, documentation, and even customer support--reverse-engineering how it all works. Our results offer rigorous support for the recent hypothesis that criticisms of the state, its leaders, and their policies are published, whereas posts about real-world events with collective action potential are censored. Copyright © 2014, American Association for the Advancement of Science.

  7. Reverse engineering of B-pillar with 3D optical scanning for manufacturing of non-uniform thickness part

    OpenAIRE

    Islam Md. Tasbirul; Abdullah A.B.; Mahmud Mohamad Zihad

    2017-01-01

    This paper presents reverse engineering (RE) of a complex automobile structural part, B-pillar. As a major part of the automobile body-in white (BiW), B-pillar has substantial opportunity for weight reduction by introducing variable thickness across its sections. To leverage such potential, an existing B-pillar was reverse engineered with a 3D optical scanner and computer aided design (CAD) application. First, digital data (i.e. in meshes) of exiting B-pillar was obtained by the scanner, and ...

  8. Reverse engineering of TLX oncogenic transcriptional networks identifies RUNX1 as tumor suppressor in T-ALL.

    Science.gov (United States)

    Della Gatta, Giusy; Palomero, Teresa; Perez-Garcia, Arianne; Ambesi-Impiombato, Alberto; Bansal, Mukesh; Carpenter, Zachary W; De Keersmaecker, Kim; Sole, Xavier; Xu, Luyao; Paietta, Elisabeth; Racevskis, Janis; Wiernik, Peter H; Rowe, Jacob M; Meijerink, Jules P; Califano, Andrea; Ferrando, Adolfo A

    2012-02-26

    The TLX1 and TLX3 transcription factor oncogenes have a key role in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). Here we used reverse engineering of global transcriptional networks to decipher the oncogenic regulatory circuit controlled by TLX1 and TLX3. This systems biology analysis defined T cell leukemia homeobox 1 (TLX1) and TLX3 as master regulators of an oncogenic transcriptional circuit governing T-ALL. Notably, a network structure analysis of this hierarchical network identified RUNX1 as a key mediator of the T-ALL induced by TLX1 and TLX3 and predicted a tumor-suppressor role for RUNX1 in T cell transformation. Consistent with these results, we identified recurrent somatic loss-of-function mutations in RUNX1 in human T-ALL. Overall, these results place TLX1 and TLX3 at the top of an oncogenic transcriptional network controlling leukemia development, show the power of network analyses to identify key elements in the regulatory circuits governing human cancer and identify RUNX1 as a tumor-suppressor gene in T-ALL.

  9. Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast.

    Science.gov (United States)

    Oud, Bart; van Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

    2012-03-01

    Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  10. Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

    Science.gov (United States)

    Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

    2017-08-17

    Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

  11. Prevention of Preharvest Sprouting through Hormone Engineering and Germination Recovery by Chemical Biology.

    Science.gov (United States)

    Nonogaki, Mariko; Nonogaki, Hiroyuki

    2017-01-01

    Vivipary, germination of seeds on the maternal plant, is observed in nature and provides ecological advantages in certain wild species, such as mangroves. However, precocious seed germination in agricultural species, such as preharvest sprouting (PHS) in cereals, is a serious issue for food security. PHS reduces grain quality and causes economical losses to farmers. PHS can be prevented by translating the basic knowledge of hormone biology in seeds into technologies. Biosynthesis of abscisic acid (ABA), which is an essential hormone for seed dormancy, can be engineered to enhance dormancy and prevent PHS. Enhancing nine- cis -epoxycarotenoid dioxygenase (NCED), a rate-limiting enzyme of ABA biosynthesis, through a chemically induced gene expression system, has successfully been used to suppress germination of Arabidopsis seeds. The more advanced system NCED positive-feedback system, which amplifies ABA biosynthesis in a seed-specific manner without chemical induction, has also been developed. The proofs of concept established in the model species are now ready to be applied to crops. A potential problem is recovery of germination from hyperdormant crop grains. Hyperdormancy induced by the NCED systems can be reversed by inducing counteracting genes, such as NCED RNA interference or gibberellin (GA) biosynthesis genes. Alternatively, seed sensitivity to ABA can be modified to rescue germination using the knowledge of chemical biology. ABA antagonists, which were developed recently, have great potential to recover germination from the hyperdormant seeds. Combination of the dormancy-imposing and -releasing approaches will establish a comprehensive technology for PHS prevention and germination recovery.

  12. Automation of reverse engineering process in aircraft modeling and related optimization problems

    Science.gov (United States)

    Li, W.; Swetits, J.

    1994-01-01

    During the year of 1994, the engineering problems in aircraft modeling were studied. The initial concern was to obtain a surface model with desirable geometric characteristics. Much of the effort during the first half of the year was to find an efficient way of solving a computationally difficult optimization model. Since the smoothing technique in the proposal 'Surface Modeling and Optimization Studies of Aerodynamic Configurations' requires solutions of a sequence of large-scale quadratic programming problems, it is important to design algorithms that can solve each quadratic program in a few interactions. This research led to three papers by Dr. W. Li, which were submitted to SIAM Journal on Optimization and Mathematical Programming. Two of these papers have been accepted for publication. Even though significant progress has been made during this phase of research and computation times was reduced from 30 min. to 2 min. for a sample problem, it was not good enough for on-line processing of digitized data points. After discussion with Dr. Robert E. Smith Jr., it was decided not to enforce shape constraints in order in order to simplify the model. As a consequence, P. Dierckx's nonparametric spline fitting approach was adopted, where one has only one control parameter for the fitting process - the error tolerance. At the same time the surface modeling software developed by Imageware was tested. Research indicated a substantially improved fitting of digitalized data points can be achieved if a proper parameterization of the spline surface is chosen. A winning strategy is to incorporate Dierckx's surface fitting with a natural parameterization for aircraft parts. The report consists of 4 chapters. Chapter 1 provides an overview of reverse engineering related to aircraft modeling and some preliminary findings of the effort in the second half of the year. Chapters 2-4 are the research results by Dr. W. Li on penalty functions and conjugate gradient methods for

  13. Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent advances and future directions.

    Science.gov (United States)

    Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Chen, Jian; Liu, Long

    By combining advanced omics technology and computational modeling, systems biologists have identified and inferred thousands of regulatory events and system-wide interactions of the bacterium Bacillus subtilis, which is commonly used both in the laboratory and in industry. This dissection of the multiple layers of regulatory networks and their interactions has provided invaluable information for unraveling regulatory mechanisms and guiding metabolic engineering. In this review, we discuss recent advances in the systems biology and metabolic engineering of B. subtilis and highlight current gaps in our understanding of global metabolism and global pathway engineering in this organism. We also propose future perspectives in the systems biology of B. subtilis and suggest ways that this approach can be used to guide metabolic engineering. Specifically, although hundreds of regulatory events have been identified or inferred via systems biology approaches, systematic investigation of the functionality of these events in vivo has lagged, thereby preventing the elucidation of regulatory mechanisms and further rational pathway engineering. In metabolic engineering, ignoring the engineering of multilayer regulation hinders metabolic flux redistribution. Post-translational engineering, allosteric engineering, and dynamic pathway analyses and control will also contribute to the modulation and control of the metabolism of engineered B. subtilis, ultimately producing the desired cellular traits. We hope this review will aid metabolic engineers in making full use of available systems biology datasets and approaches for the design and perfection of microbial cell factories through global metabolism optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Reverse engineering of wörner type drilling machine structure.

    Science.gov (United States)

    Wibowo, A.; Belly, I.; llhamsyah, R.; Indrawanto; Yuwana, Y.

    2018-03-01

    A product design needs to be modified based on the conditions of production facilities and existing resource capabilities without reducing the functional aspects of the product itself. This paper describes the reverse engineering process of the main structure of the wörner type drilling machine to obtain a machine structure design that can be made by resources with limited ability by using simple processes. Some structural, functional and the work mechanism analyzes have been performed to understand the function and role of each basic components. The process of dismantling of the drilling machine and measuring each of the basic components was performed to obtain sets of the geometry and size data of each component. The geometric model of each structure components and the machine assembly were built to facilitate the simulation process and machine performance analysis that refers to ISO standard of drilling machine. The tolerance stackup analysis also performed to determine the type and value of geometrical and dimensional tolerances, which could affect the ease of the components to be manufactured and assembled

  15. A data-driven approach to reverse engineering customer engagement models: towards functional constructs.

    Directory of Open Access Journals (Sweden)

    Natalie Jane de Vries

    Full Text Available Online consumer behavior in general and online customer engagement with brands in particular, has become a major focus of research activity fuelled by the exponential increase of interactive functions of the internet and social media platforms and applications. Current research in this area is mostly hypothesis-driven and much debate about the concept of Customer Engagement and its related constructs remains existent in the literature. In this paper, we aim to propose a novel methodology for reverse engineering a consumer behavior model for online customer engagement, based on a computational and data-driven perspective. This methodology could be generalized and prove useful for future research in the fields of consumer behaviors using questionnaire data or studies investigating other types of human behaviors. The method we propose contains five main stages; symbolic regression analysis, graph building, community detection, evaluation of results and finally, investigation of directed cycles and common feedback loops. The 'communities' of questionnaire items that emerge from our community detection method form possible 'functional constructs' inferred from data rather than assumed from literature and theory. Our results show consistent partitioning of questionnaire items into such 'functional constructs' suggesting the method proposed here could be adopted as a new data-driven way of human behavior modeling.

  16. Engineering and physics of high-power-density, compact, reversed-field-pinch fusion reactors

    International Nuclear Information System (INIS)

    Najmabadi, F.; Conn, R.W.; Krakowski, R.A.; Schultz, K.R.; Steiner, D.

    1989-01-01

    The technical feasibility and key developmental issues of compact, high-power-density Reversed-Field-Pinch (RFP) reactors are the primary results of the TITAN RFP reactor study. Two design approaches emerged, TITAN-I and TITAN-II, both of which are steady-state, DT-burning, circa 1000 MWe power reactors. The TITAN designs are physically compact and have a high neutron wall loading of 18 MW m 2 . Detailed analyses indicate that: a) each design is technically feasible; b) attractive features of compact RFP reactors can be realized without sacrificing the safety and environmental potential of fusion; and c) major features of this particular embodiment of the RFP reactor are retained in a design window of neutron wall loading ranging from 10 to 20 MW/m 2 . A major product of the TITAN study is the identification and quantification of major engineering and physics requirements for this class of RFP reactors. These findings are the focus of this paper. (author). 26 refs.; 4 figs.; 1 tab

  17. A data-driven approach to reverse engineering customer engagement models: towards functional constructs.

    Science.gov (United States)

    de Vries, Natalie Jane; Carlson, Jamie; Moscato, Pablo

    2014-01-01

    Online consumer behavior in general and online customer engagement with brands in particular, has become a major focus of research activity fuelled by the exponential increase of interactive functions of the internet and social media platforms and applications. Current research in this area is mostly hypothesis-driven and much debate about the concept of Customer Engagement and its related constructs remains existent in the literature. In this paper, we aim to propose a novel methodology for reverse engineering a consumer behavior model for online customer engagement, based on a computational and data-driven perspective. This methodology could be generalized and prove useful for future research in the fields of consumer behaviors using questionnaire data or studies investigating other types of human behaviors. The method we propose contains five main stages; symbolic regression analysis, graph building, community detection, evaluation of results and finally, investigation of directed cycles and common feedback loops. The 'communities' of questionnaire items that emerge from our community detection method form possible 'functional constructs' inferred from data rather than assumed from literature and theory. Our results show consistent partitioning of questionnaire items into such 'functional constructs' suggesting the method proposed here could be adopted as a new data-driven way of human behavior modeling.

  18. An Integrated Reverse Engineering Approach for Accuracy Control of Free-Form Objects

    Directory of Open Access Journals (Sweden)

    Pathak Vimal Kumar

    2016-12-01

    Full Text Available Computer-aided tools help in shortening and eradicating numerous repetitive tasks that reduces the gap between digital model and actual product. Use of these tools assists in realizing free-form objects such as custom fit products as described by a stringent interaction with the human body. Development of such a model presents a challenging situation for reverse engineering (RE which is not analogous with the requirement for generating simple geometric models. Hence, an alternating way of producing more accurate three-dimensional models is proposed. For creating accurate 3D models, point clouds are processed through filtering, segmentation, mesh smoothing and surface generation. These processes help in converting the initial unorganized point data into a 3D digital model and simultaneously influence the quality of model. This study provides an optimum balance for the best accuracy obtainable with maximum allowable deviation to lessen computer handling and processing time. A realistic non trivial case study of free-form prosthetic socket is considered. The accuracy obtained for the developed model is acceptable for the use in medical applications and FEM analysis.

  19. An Analytical Reverse Engineering of IELTS Listening Tasks for a Construct Model

    Directory of Open Access Journals (Sweden)

    Masood Khalili Sabet

    2017-10-01

    Full Text Available The study reported here was concerned with the issue of reverse engineering of language test items as it relates to the identification of the language constructs underlying listening tasks of LELTS test. In this regard, the IELTS examination papers, from IELTS 1 to IELTS 10 were compiled as a corpus for the analysis. Tasks were analyzed using a taxonomic frame work adopted from Moore, Morton and price (2012, that was originally adapted from Weir and Urquhart (1998, with a focus on two dimensions of difference: level of engagement, referring to the level of text with which a listener required to engage in order to respond to a task (local vs. global; type of engagement referring to the way (or ways  listeners expected to engage with a text in order to process the material to respond to a task (literal vs. interpretative. Overall, the analysis found evidences of bottom up processing underlying most IELTS listening tasks. The majority of tasks were identified to have a ‘local-literal’ configuration on their orientation, demanding primarily a basic understanding of relatively small textual units of the material. The results of the study were used to suggest the practical implications for the four groups of the people involved in the IELTS educational contexts: participants; teachers; material preparation experts, and curriculum designers.

  20. Engineered reversal of drug resistance in cancer cells--metastases suppressor factors as change agents.

    Science.gov (United States)

    Yadav, Vinod Kumar; Kumar, Akinchan; Mann, Anita; Aggarwal, Suruchi; Kumar, Maneesh; Roy, Sumitabho Deb; Pore, Subrata Kumar; Banerjee, Rajkumar; Mahesh Kumar, Jerald; Thakur, Ram Krishna; Chowdhury, Shantanu

    2014-01-01

    Building molecular correlates of drug resistance in cancer and exploiting them for therapeutic intervention remains a pressing clinical need. To identify factors that impact drug resistance herein we built a model that couples inherent cell-based response toward drugs with transcriptomes of resistant/sensitive cells. To test this model, we focused on a group of genes called metastasis suppressor genes (MSGs) that influence aggressiveness and metastatic potential of cancers. Interestingly, modeling of 84 000 drug response transcriptome combinations predicted multiple MSGs to be associated with resistance of different cell types and drugs. As a case study, on inducing MSG levels in a drug resistant breast cancer line resistance to anticancer drugs caerulomycin, camptothecin and topotecan decreased by more than 50-60%, in both culture conditions and also in tumors generated in mice, in contrast to control un-induced cells. To our knowledge, this is the first demonstration of engineered reversal of drug resistance in cancer cells based on a model that exploits inherent cellular response profiles.

  1. A Critical Analysis of a Hand Orthosis Reverse Engineering and 3D Printing Process

    Directory of Open Access Journals (Sweden)

    Gabriele Baronio

    2016-01-01

    Full Text Available The possibility to realize highly customized orthoses is receiving boost thanks to the widespread diffusion of low-cost 3D printing technologies. However, rapid prototyping (RP with 3D printers is only the final stage of patient personalized orthotics processes. A reverse engineering (RE process is in fact essential before RP, to digitize the 3D anatomy of interest and to process the obtained surface with suitable modeling software, in order to produce the virtual solid model of the orthosis to be printed. In this paper, we focus on the specific and demanding case of the customized production of hand orthosis. We design and test the essential steps of the entire production process with particular emphasis on the accurate acquisition of the forearm geometry and on the subsequent production of a printable model of the orthosis. The choice of the various hardware and software tools (3D scanner, modeling software, and FDM printer is aimed at the mitigation of the design and production costs while guaranteeing suitable levels of data accuracy, process efficiency, and design versatility. Eventually, the proposed method is critically analyzed so that the residual issues and critical aspects are highlighted in order to discuss possible alternative approaches and to derive insightful observations that could guide future research activities.

  2. Design of microreactor by integration of reverse engineering and direct metal laser sintering process

    Energy Technology Data Exchange (ETDEWEB)

    Bineli, Aulus Roberto Romao; Gimenez Perez, Ana Paula; Bernardes, Luiz Fernando; Munhoz, Andre Luiz Jardini; Maciel Filho, Rubens [Universidade de Campinas (LOPCA/UNICAMP), SP (Brazil). School of Chemical Engineering. Laboratory of Optimization, Design and Advanced Process Control], Email: aulus@feq.unicamp.br

    2010-07-01

    The propose of this work is to present high precision microfabrication facilities using computer aided technologies as Reverse Engineering (RE) and Rapid Manufacturing (RM) to analyze, design and construct micro reactors to produce high content hydrogen gas. Micro reactors are very compact, have a high surface to volume ratio, exhibit enhanced heat and mass transfer rates, denotes extremely low pressure drop and allow improved thermal integration in the processes involved. The main goals of micro reactors are the optimization of conventional chemical plants and low footprint, opening different ways to research new process technologies and synthesis of new products. In this work, a microchannels plate and housing structure of these plates were fabricated using DMLS method (Direct Metal Laser Sintering). The plates were analyzed to verify the minimum thickness wall that machine can produce, and the housing structure were digitalized, using a 3D scanning, to perform a 3D inspection and to verify the deflection of the constructed part in comparison with original CAD design models. It was observed that DMLS systems are able to produce micro reactors and microchannels plates with high precision at different metallic materials. However, it is important to choose appropriate conditions to avoid residual stresses and consequently warping parts. (author)

  3. Metabolic engineering with systems biology tools to optimize production of prokaryotic secondary metabolites

    DEFF Research Database (Denmark)

    Kim, Hyun Uk; Charusanti, Pep; Lee, Sang Yup

    2016-01-01

    Metabolic engineering using systems biology tools is increasingly applied to overproduce secondary metabolites for their potential industrial production. In this Highlight, recent relevant metabolic engineering studies are analyzed with emphasis on host selection and engineering approaches...... for the optimal production of various prokaryotic secondary metabolites: native versus heterologous hosts (e.g., Escherichia coli) and rational versus random approaches. This comparative analysis is followed by discussions on systems biology tools deployed in optimizing the production of secondary metabolites....... The potential contributions of additional systems biology tools are also discussed in the context of current challenges encountered during optimization of secondary metabolite production....

  4. Designing a 'neotissue' using the principles of biology, chemistry and engineering.

    Science.gov (United States)

    Nannaparaju, Madhusudhan; Oragui, Emeka; Khan, Wasim S

    2012-01-01

    The traditional methods of treating musculoskeletal injuries and disorders are not completely effective and have several limitations. Tissue engineering involves using the principles of biology, chemistry and engineering to design a 'neotissue' that augments a malfunctioning in vivo tissue. The main requirements for functional engineered tissue include reparative cellular components that proliferate on a scaffold grown within a bioreactor that provides specific biochemical and physical signals to regulate cell differentiation and tissue assembly. In this review we provide an overview of the biology of common musculoskeletal tissue and discuss their common pathologies. We also describe the commonly used stem cells, scaffolds and bioreactors and evaluate their role in issue engineering.

  5. Creating to understand – developmental biology meets engineering in Paris

    NARCIS (Netherlands)

    Kicheva, Anna; Rivron, Nicolas C.

    2017-01-01

    In November 2016, developmental biologists, synthetic biologists and engineers gathered in Paris for a meeting called ‘Engineering the embryo’. The participants shared an interest in exploring how synthetic systems can reveal new principles of embryonic development, and how the in vitro manipulation

  6. 6th European Conference of the International Federation for Medical and Biological Engineering

    CERN Document Server

    Vasic, Darko

    2015-01-01

    This volume presents the Proceedings of the 6th European Conference of the International Federation for Medical and Biological Engineering (MBEC2014), held in Dubrovnik September 7 – 11, 2014. The general theme of MBEC 2014 is "Towards new horizons in biomedical engineering" The scientific discussions in these conference proceedings include the following themes: - Biomedical Signal Processing - Biomedical Imaging and Image Processing - Biosensors and Bioinstrumentation - Bio-Micro/Nano Technologies - Biomaterials - Biomechanics, Robotics and Minimally Invasive Surgery - Cardiovascular, Respiratory and Endocrine Systems Engineering - Neural and Rehabilitation Engineering - Molecular, Cellular and Tissue Engineering - Bioinformatics and Computational Biology - Clinical Engineering and Health Technology Assessment - Health Informatics, E-Health and Telemedicine - Biomedical Engineering Education

  7. Reverse engineering of modified genes by Bayesian network analysis defines molecular determinants critical to the development of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Brian W Kunkle

    Full Text Available In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV, and 'key genes' within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated. These 10 genes were able to predict tumor status with 96-100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential 'hubs of activity'. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several 'key genes' may be required for the development of glioblastoma. Further studies are needed to validate these 'key genes' as useful tools for early detection and novel therapeutic options for these tumors.

  8. The necessity of a theory of biology for tissue engineering: metabolism-repair systems.

    Science.gov (United States)

    Ganguli, Suman; Hunt, C Anthony

    2004-01-01

    Since there is no widely accepted global theory of biology, tissue engineering and bioengineering lack a theoretical understanding of the systems being engineered. By default, tissue engineering operates with a "reductionist" theoretical approach, inherited from traditional engineering of non-living materials. Long term, that approach is inadequate, since it ignores essential aspects of biology. Metabolism-repair systems are a theoretical framework which explicitly represents two "functional" aspects of living organisms: self-repair and self-replication. Since repair and replication are central to tissue engineering, we advance metabolism-repair systems as a potential theoretical framework for tissue engineering. We present an overview of the framework, and indicate directions to pursue for extending it to the context of tissue engineering. We focus on biological networks, both metabolic and cellular, as one such direction. The construction of these networks, in turn, depends on biological protocols. Together these concepts may help point the way to a global theory of biology appropriate for tissue engineering.

  9. Comparing Two Definitions of Work for a Biological Quantum Heat Engine

    International Nuclear Information System (INIS)

    Xu You-Yang; Zhao Shun-Cai; Liu Juan

    2015-01-01

    Systems of photosynthetic reaction centres have been modelled as heat engines, while it has also been reported that the efficiency and power of such heat engines can be enhanced by quantum interference — a trait that has attracted much interest. We compare two definitions of the work of such a photosynthetic heat engine, i.e. definition A used by Weimer et al. and B by Dorfman et al. We also introduce a coherent interaction between donor and acceptor (CIDA) to demonstrate a reversible energy transport. We show that these two definitions of work can impart contradictory results, that is, CIDA enhances the power and efficiency of the photosynthetic heat engine with definition B but not with A. Additionally, we find that both reversible and irreversible excitation-energy transport can be described with definition A, but definition B can only model irreversible transport. As a result, we conclude that definition A is more suitable for photosynthetic systems than definition B. (paper)

  10. Introducing Molecular Biology to Environmental Engineers through Development of a New Course.

    Science.gov (United States)

    Oerther, Daniel B.

    2002-01-01

    Introduces a molecular biology course designed for environmental engineering majors using 16S ribosomal ribonucleic acid-targeted technology that allows students to identify and study microorganisms in bioreactor environments. (Contains 17 references.) (YDS)

  11. Reverse Engineering and Security Evaluation of Commercial Tags for RFID-Based IoT Applications.

    Science.gov (United States)

    Fernández-Caramés, Tiago M; Fraga-Lamas, Paula; Suárez-Albela, Manuel; Castedo, Luis

    2016-12-24

    The Internet of Things (IoT) is a distributed system of physical objects that requires the seamless integration of hardware (e.g., sensors, actuators, electronics) and network communications in order to collect and exchange data. IoT smart objects need to be somehow identified to determine the origin of the data and to automatically detect the elements around us. One of the best positioned technologies to perform identification is RFID (Radio Frequency Identification), which in the last years has gained a lot of popularity in applications like access control, payment cards or logistics. Despite its popularity, RFID security has not been properly handled in numerous applications. To foster security in such applications, this article includes three main contributions. First, in order to establish the basics, a detailed review of the most common flaws found in RFID-based IoT systems is provided, including the latest attacks described in the literature. Second, a novel methodology that eases the detection and mitigation of such flaws is presented. Third, the latest RFID security tools are analyzed and the methodology proposed is applied through one of them (Proxmark 3) to validate it. Thus, the methodology is tested in different scenarios where tags are commonly used for identification. In such systems it was possible to clone transponders, extract information, and even emulate both tags and readers. Therefore, it is shown that the methodology proposed is useful for auditing security and reverse engineering RFID communications in IoT applications. It must be noted that, although this paper is aimed at fostering RFID communications security in IoT applications, the methodology can be applied to any RFID communications protocol.

  12. Reverse Engineering and Security Evaluation of Commercial Tags for RFID-Based IoT Applications

    Directory of Open Access Journals (Sweden)

    Tiago M. Fernández-Caramés

    2016-12-01

    Full Text Available The Internet of Things (IoT is a distributed system of physical objects that requires the seamless integration of hardware (e.g., sensors, actuators, electronics and network communications in order to collect and exchange data. IoT smart objects need to be somehow identified to determine the origin of the data and to automatically detect the elements around us. One of the best positioned technologies to perform identification is RFID (Radio Frequency Identification, which in the last years has gained a lot of popularity in applications like access control, payment cards or logistics. Despite its popularity, RFID security has not been properly handled in numerous applications. To foster security in such applications, this article includes three main contributions. First, in order to establish the basics, a detailed review of the most common flaws found in RFID-based IoT systems is provided, including the latest attacks described in the literature. Second, a novel methodology that eases the detection and mitigation of such flaws is presented. Third, the latest RFID security tools are analyzed and the methodology proposed is applied through one of them (Proxmark 3 to validate it. Thus, the methodology is tested in different scenarios where tags are commonly used for identification. In such systems it was possible to clone transponders, extract information, and even emulate both tags and readers. Therefore, it is shown that the methodology proposed is useful for auditing security and reverse engineering RFID communications in IoT applications. It must be noted that, although this paper is aimed at fostering RFID communications security in IoT applications, the methodology can be applied to any RFID communications protocol.

  13. Effect of engineered environment on microbial community structure in biofilter and biofilm on reverse osmosis membrane.

    Science.gov (United States)

    Jeong, Sanghyun; Cho, Kyungjin; Jeong, Dawoon; Lee, Seockheon; Leiknes, TorOve; Vigneswaran, Saravanamuthu; Bae, Hyokwan

    2017-11-01

    Four dual media filters (DMFs) were operated in a biofiltration mode with different engineered environments (DMF I and II: coagulation with/without acidification and DMF III and IV: without/with chlorination). Designed biofilm enrichment reactors (BERs) containing the removable reverse osmosis (RO) coupons, were connected at the end of the DMFs in parallel to analyze the biofilm on the RO membrane by DMF effluents. Filtration performances were evaluated in terms of dissolved organic carbon (DOC) and assimilable organic carbon (AOC). Organic foulants on the RO membrane were also quantified and fractionized. The bacterial community structures in liquid (seawater and effluent) and biofilm (DMF and RO) samples were analyzed using 454-pyrosequencing. The DMF IV fed with the chlorinated seawater demonstrated the highest reductions of DOC including LMW-N as well as AOC among the other DMFs. The DMF IV was also effective in reducing organic foulants on the RO membrane surface. The bacterial community structure was grouped according to the sample phase (i.e., liquid and biofilm samples), sampling location (i.e., DMF and RO samples), and chlorination (chlorinated and non-chlorinated samples). In particular, the biofilm community in the DMF IV differed from the other DMF treatments, suggesting that chlorination exerted as stronger selective pressure than pH adjustment or coagulation on the biofilm community. In the DMF IV, several chemoorganotrophic chlorine-resistant biofilm-forming bacteria such as Hyphomonas, Erythrobacter, and Sphingomonas were predominant, and they may enhance organic carbon degradation efficiency. Diverse halophilic or halotolerant organic degraders were also found in other DMFs (i.e., DMF I, II, and III). Various kinds of dominant biofilm-forming bacteria were also investigated in RO membrane samples; the results provided possible candidates that cause biofouling when DMF process is applied as the pretreatment option for the RO process. Copyright

  14. Social smile reproducibility using 3-D stereophotogrammetry and reverse engineering technology.

    Science.gov (United States)

    Dindaroğlu, Furkan; Duran, Gökhan Serhat; Görgülü, Serkan; Yetkiner, Enver

    2016-05-01

    To assess the range of social smile reproducibility using 3-D stereophotogrammetry and reverse engineering technology. Social smile images of white adolescents (N  =  15, mean age  =  15.4 ±1.5 years; range  =  14-17 years) were obtained using 3dMDFlex (3dMD, Atlanta, Ga). Each participant was asked to produce 16 social smiles at 3-minute intervals. All images were obtained in natural head position. Alignment of images, segmentation of smile area, and 3-D deviation analysis were carried out using Geomagic Control software (3D Systems Inc, Cary, NC). A single image was taken as a reference, and the remaining 15 images were compared with the reference image to evaluate positive and negative deviations. The differences between the mean deviation limits of participants with the highest and the lowest deviations and the total mean deviations were evaluated using Bland-Altman Plots. Minimum and maximum deviations of a single image from the reference image were 0.34 and 2.69 mm, respectively. Lowest deviation between two images was within 0.5 mm and 1.54 mm among all participants (mean, 0.96 ± 0.21 mm), and the highest deviation was between 0.41 mm and 2.69 mm (mean, 1.53 ± 0.46 mm). For a single patient, when all alignments were considered together, the mean deviation was between 0.32 ± 0.10 mm and 0.59 ± 0.24 mm. Mean deviation for one image was between 0.14 and 1.21 mm. The range of reproducibility of the social smile presented individual variability, but this variation was not clinically significant or detectable under routine clinical observation.

  15. Design and manufacture of customized dental implants by using reverse engineering and selective laser melting technology.

    Science.gov (United States)

    Chen, Jianyu; Zhang, Zhiguang; Chen, Xianshuai; Zhang, Chunyu; Zhang, Gong; Xu, Zhewu

    2014-11-01

    Recently a new therapeutic concept of patient-specific implant dentistry has been advanced based on computer-aided design/computer-aided manufacturing technology. However, a comprehensive study of the design and 3-dimensional (3D) printing of the customized implants, their mechanical properties, and their biomechanical behavior is lacking. The purpose of this study was to evaluate the mechanical and biomechanical performance of a novel custom-made dental implant fabricated by the selective laser melting technique with simulation and in vitro experimental studies. Two types of customized implants were designed by using reverse engineering: a root-analog implant and a root-analog threaded implant. The titanium implants were printed layer by layer with the selective laser melting technique. The relative density, surface roughness, tensile properties, bend strength, and dimensional accuracy of the specimens were evaluated. Nonlinear and linear finite element analysis and experimental studies were used to investigate the stress distribution, micromotion, and primary stability of the implants. Selective laser melting 3D printing technology was able to reproduce the customized implant designs and produce high density and strength and adequate dimensional accuracy. Better stress distribution and lower maximum micromotions were observed for the root-analog threaded implant model than for the root-analog implant model. In the experimental tests, the implant stability quotient and pull-out strength of the 2 types of implants indicated that better primary stability can be obtained with a root-analog threaded implant design. Selective laser melting proved to be an efficient means of printing fully dense customized implants with high strength and sufficient dimensional accuracy. Adding the threaded characteristic to the customized root-analog threaded implant design maintained the approximate geometry of the natural root and exhibited better stress distribution and

  16. Effect of engineered environment on microbial community structure in biofilter and biofilm on reverse osmosis membrane

    KAUST Repository

    Jeong, Sanghyun

    2017-07-25

    Four dual media filters (DMFs) were operated in a biofiltration mode with different engineered environments (DMF I and II: coagulation with/without acidification and DMF III and IV: without/with chlorination). Designed biofilm enrichment reactors (BERs) containing the removable reverse osmosis (RO) coupons, were connected at the end of the DMFs in parallel to analyze the biofilm on the RO membrane by DMF effluents. Filtration performances were evaluated in terms of dissolved organic carbon (DOC) and assimilable organic carbon (AOC). Organic foulants on the RO membrane were also quantified and fractionized. The bacterial community structures in liquid (seawater and effluent) and biofilm (DMF and RO) samples were analyzed using 454-pyrosequencing. The DMF IV fed with the chlorinated seawater demonstrated the highest reductions of DOC including LMW-N as well as AOC among the other DMFs. The DMF IV was also effective in reducing organic foulants on the RO membrane surface. The bacterial community structure was grouped according to the sample phase (i.e., liquid and biofilm samples), sampling location (i.e., DMF and RO samples), and chlorination (chlorinated and non-chlorinated samples). In particular, the biofilm community in the DMF IV differed from the other DMF treatments, suggesting that chlorination exerted as stronger selective pressure than pH adjustment or coagulation on the biofilm community. In the DMF IV, several chemoorganotrophic chlorine-resistant biofilm-forming bacteria such as Hyphomonas, Erythrobacter, and Sphingomonas were predominant, and they may enhance organic carbon degradation efficiency. Diverse halophilic or halotolerant organic degraders were also found in other DMFs (i.e., DMF I, II, and III). Various kinds of dominant biofilm-forming bacteria were also investigated in RO membrane samples; the results provided possible candidates that cause biofouling when DMF process is applied as the pretreatment option for the RO process.

  17. Reverse Engineering and Security Evaluation of Commercial Tags for RFID-Based IoT Applications

    Science.gov (United States)

    Fernández-Caramés, Tiago M.; Fraga-Lamas, Paula; Suárez-Albela, Manuel; Castedo, Luis

    2016-01-01

    The Internet of Things (IoT) is a distributed system of physical objects that requires the seamless integration of hardware (e.g., sensors, actuators, electronics) and network communications in order to collect and exchange data. IoT smart objects need to be somehow identified to determine the origin of the data and to automatically detect the elements around us. One of the best positioned technologies to perform identification is RFID (Radio Frequency Identification), which in the last years has gained a lot of popularity in applications like access control, payment cards or logistics. Despite its popularity, RFID security has not been properly handled in numerous applications. To foster security in such applications, this article includes three main contributions. First, in order to establish the basics, a detailed review of the most common flaws found in RFID-based IoT systems is provided, including the latest attacks described in the literature. Second, a novel methodology that eases the detection and mitigation of such flaws is presented. Third, the latest RFID security tools are analyzed and the methodology proposed is applied through one of them (Proxmark 3) to validate it. Thus, the methodology is tested in different scenarios where tags are commonly used for identification. In such systems it was possible to clone transponders, extract information, and even emulate both tags and readers. Therefore, it is shown that the methodology proposed is useful for auditing security and reverse engineering RFID communications in IoT applications. It must be noted that, although this paper is aimed at fostering RFID communications security in IoT applications, the methodology can be applied to any RFID communications protocol. PMID:28029119

  18. Engineering Design of an Adaptive Leg Prosthesis Using Biological Principles

    DEFF Research Database (Denmark)

    Lenau, Torben Anker; Dentel, Andy; Invarsdottir, Thorunn

    2010-01-01

    The biomimetic design process is explored through a design case: An adaptive leg prosthesis. The aim is to investigate if the biomimetic design process can be carried out with a minimum of biological knowledge and without using advanced design methods. In the design case biomimetic design was suc...... was successfully carried out using library search resulting in 14 biological analogies for the design problem 'shape adaption'. It is proposed that search results are handled using special cards describing the biological phenomena and the functional principles....

  19. A Survey of Automatic Protocol Reverse Engineering Approaches, Methods, and Tools on the Inputs and Outputs View

    OpenAIRE

    Baraka D. Sija; Young-Hoon Goo; Kyu-Seok Shim; Huru Hasanova; Myung-Sup Kim

    2018-01-01

    A network protocol defines rules that control communications between two or more machines on the Internet, whereas Automatic Protocol Reverse Engineering (APRE) defines the way of extracting the structure of a network protocol without accessing its specifications. Enough knowledge on undocumented protocols is essential for security purposes, network policy implementation, and management of network resources. This paper reviews and analyzes a total of 39 approaches, methods, and tools towards ...

  20. Advancing the science of forest hydrology A challenge to agricultural and biological engineers

    Science.gov (United States)

    Devendra Amatya; Wayne Skaggs; Carl Trettin

    2009-01-01

    For more than a century, agricultural and biological engineers have provided major advances in science, engineering, and technology to increase food and fiber production to meet the demands of a rapidly growing global population. The land base for these technological advances has originated largely from forested lands, which have experienced dramatic declines over the...

  1. Reverse engineering of heavy-ion collisions: Unraveling initial conditions from anisotropic flow data

    International Nuclear Information System (INIS)

    Retinskaya, Ekaterina

    2014-01-01

    Ultra-Relativistic heavy-ion physics is a promising field of high energy physics connecting two fields: nuclear physics and elementary particle physics. Experimental achievements of the last years have provided an opportunity to study the properties of a new state of matter created in heavy-ion collisions called quark-gluon plasma. The initial state of two colliding nuclei is affected by fluctuations coming from wave- functions of nucleons. These fluctuations lead to the momentum anisotropy of the hadronic matter which is observed by the detectors. The system created in the collision behaves like a fluid, so the initial state is connected to the final state via hydrodynamic evolution. In this thesis we model the evolution with relativistic viscous hydrodynamics. Our results, combined with experimental data, give non trivial constraints on the initial state, thus achieving 'reverse engineering' of the heavy-ion collisions. The observable which characterizes the momentum anisotropy is the anisotropic flow v n . We present the first measurements of the first harmonic of the anisotropic flow called directed flow v 1 in Pb-Pb collisions at the LHC. We then perform the first viscous hydrodynamic modeling of directed flow and show that it is less sensitive to viscosity than higher harmonics. Comparison of these experimental data with the modeling allows to extract the values of the dipole asymmetry of the initial state, which provides constraints on the models of initial states. A prediction for directed flow v 1 in Au-Au collisions is also made for RHIC. We then perform a similar modeling of the second and third harmonics of the anisotropic flow, called respectively elliptic v 2 and triangular v 3 flow. A combined analysis of the elliptic and triangular flow data compared with viscous hydrodynamic calculations allows us to put constraints on initial ellipticity and triangularity of the system. These constraints are then used as a filter for different models of

  2. Review of Microfluidic Photobioreactor Technology for Metabolic Engineering and Synthetic Biology of Cyanobacteria and Microalgae

    Directory of Open Access Journals (Sweden)

    Ya-Tang Yang

    2016-10-01

    Full Text Available One goal of metabolic engineering and synthetic biology for cyanobacteria and microalgae is to engineer strains that can optimally produce biofuels and commodity chemicals. However, the current workflow is slow and labor intensive with respect to assembly of genetic parts and characterization of production yields because of the slow growth rates of these organisms. Here, we review recent progress in the microfluidic photobioreactors and identify opportunities and unmet needs in metabolic engineering and synthetic biology. Because of the unprecedented experimental resolution down to the single cell level, long-term real-time monitoring capability, and high throughput with low cost, microfluidic photobioreactor technology will be an indispensible tool to speed up the development process, advance fundamental knowledge, and realize the full potential of metabolic engineering and synthetic biology for cyanobacteria and microalgae.

  3. Cell-free protein synthesis enabled rapid prototyping for metabolic engineering and synthetic biology

    Directory of Open Access Journals (Sweden)

    Lihong Jiang

    2018-06-01

    Full Text Available Advances in metabolic engineering and synthetic biology have facilitated the manufacturing of many valuable-added compounds and commodity chemicals using microbial cell factories in the past decade. However, due to complexity of cellular metabolism, the optimization of metabolic pathways for maximal production represents a grand challenge and an unavoidable barrier for metabolic engineering. Recently, cell-free protein synthesis system (CFPS has been emerging as an enabling alternative to address challenges in biomanufacturing. This review summarizes the recent progresses of CFPS in rapid prototyping of biosynthetic pathways and genetic circuits (biosensors to speed up design-build-test (DBT cycles of metabolic engineering and synthetic biology. Keywords: Cell-free protein synthesis, Metabolic pathway optimization, Genetic circuits, Metabolic engineering, Synthetic biology

  4. Biological responses to acidification reversal in Cumbrian streamwaters - stream water chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Tipping, E.; Hardie, D.J.; Lawlor, A.J.; Lofts, S.; Simon, B.M.; Vincent, C.D. [Institute of Freshwater Ecology, Ambleside (United Kingdom)

    1999-07-01

    This reports summarises the findings of a study sampling the streams for invertebrates and comparing the results with those made in the 1960s and 1970s, The distribution of the bacterium Cytophaga was examined, and the results of the chemical analysis of the stream waters were compared with the results from previous years. The background to the study is traced, and details of the sampling and chemical analysis are given. Evidence of the reversal of acidification in the streams is considered.

  5. The Science of Solubility: Using Reverse Engineering to Brew a Perfect Cup of Coffee

    Science.gov (United States)

    West, Andrew B.; Sickel, Aaron J.; Cribbs, Jennifer D.

    2015-01-01

    The Next Generation Science Standards call for the integration of science and engineering. Often, the introduction of engineering activities occurs after instruction in the science content. That is, engineering is used as a way for students to elaborate on science ideas that have already been explored. However, using only this sequence of…

  6. Flight Measurements of the Effect of a Controllable Thrust Reverser on the Flight Characteristics of a Single-Engine Jet Airplane

    Science.gov (United States)

    Anderson, Seth B.; Cooper, George E.; Faye, Alan E., Jr.

    1959-01-01

    A flight investigation was undertaken to determine the effect of a fully controllable thrust reverser on the flight characteristics of a single-engine jet airplane. Tests were made using a cylindrical target-type reverser actuated by a hydraulic cylinder through a "beep-type" cockpit control mounted at the base of the throttle. The thrust reverser was evaluated as an in-flight decelerating device, as a flight path control and airspeed control in landing approach, and as a braking device during the ground roll. Full deflection of the reverser for one reverser configuration resulted in a reverse thrust ratio of as much as 85 percent, which at maximum engine power corresponded to a reversed thrust of 5100 pounds. Use of the reverser in landing approach made possible a wide selection of approach angles, a large reduction in approach speed at steep approach angles, improved control of flight path angle, and more accuracy in hitting a given touchdown point. The use of the reverser as a speed brake at lower airspeeds was compromised by a longitudinal trim change. At the lower airspeeds and higher engine powers there was insufficient elevator power to overcome the nose-down trim change at full reverser deflection.

  7. A discussion of molecular biology methods for protein engineering

    CSIR Research Space (South Africa)

    Zawaira, A

    2011-09-01

    Full Text Available A number of molecular biology techniques are available to generate variants from a particular start gene for eventual protein expression. The authors discuss the basic principles of these methods in a repertoire that may be used to achieve...

  8. Micropropagation, genetic engineering, and molecular biology of Populus

    Science.gov (United States)

    N. B. Klopfenstein; Y. W. Chun; M. -S. Kim; M. A. Ahuja; M. C. Dillon; R. C. Carman; L. G. Eskew

    1997-01-01

    Thirty-four Populus biotechnology chapters, written by 85 authors, are comprised in 5 sections: 1) in vitro culture (micropropagation, somatic embryogenesis, protoplasts, somaclonal variation, and germplasm preservation); 2) transformation and foreign gene expression; 3) molecular biology (molecular/genetic characterization); 4) biotic and abiotic resistance (disease,...

  9. Importance of systems biology in engineering microbes for biofuel production

    Energy Technology Data Exchange (ETDEWEB)

    Mukhopadhyay, Aindrila; Redding, Alyssa M.; Rutherford, Becky J.; Keasling, Jay D.

    2009-12-02

    Microorganisms have been rich sources for natural products, some of which have found use as fuels, commodity chemicals, specialty chemicals, polymers, and drugs, to name a few. The recent interest in production of transportation fuels from renewable resources has catalyzed numerous research endeavors that focus on developing microbial systems for production of such natural products. Eliminating bottlenecks in microbial metabolic pathways and alleviating the stresses due to production of these chemicals are crucial in the generation of robust and efficient production hosts. The use of systems-level studies makes it possible to comprehensively understand the impact of pathway engineering within the context of the entire host metabolism, to diagnose stresses due to product synthesis, and provides the rationale to cost-effectively engineer optimal industrial microorganisms.

  10. Research and engineering assessment of biological solubilization of phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, R.D.; McIlwain, M.E.; Losinski, S.J.; Taylor, D.D.

    1993-03-01

    This research and engineering assessment examined a microbial phosphate solubilization process as a method of recovering phosphate from phosphorus containing ore compared to the existing wet acid and electric arc methods. A total of 860 microbial isolates, collected from a range of natural environments were tested for their ability to solubilize phosphate from rock phosphate. A bacterium (Pseudomonas cepacia) was selected for extensive characterization and evaluation of the mechanism of phosphate solubilization and of process engineering parameters necessary to recover phosphate from rock phosphate. These studies found that concentration of hydrogen ion and production of organic acids arising from oxidation of the carbon source facilitated microbial solubilization of both pure chemical insoluble phosphate compounds and phosphate rock. Genetic studies found that phosphate solubilization was linked to an enzyme system (glucose dehydrogenase). Process-related studies found that a critical solids density of 1% by weight (ore to liquid) was necessary for optimal solubilization. An engineering analysis evaluated the cost and energy requirements for a 2 million ton per year sized plant, whose size was selected to be comparable to existing wet acid plants.

  11. Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Science.gov (United States)

    2015-12-01

    yield stability. Transgenic approach plays an important role in crop improvement. Currently, transgenes are randomly inserted into maize genome...Improve Microbial Biofuel Production - Mary Dunlop, University of Vermont 2:30-3:00 PM Targeted Integration of Genes into the Maize Genome Facilitated...highlights gaps in the present understanding of M13 biology. Understanding the subtleties of regulation will be important for maximally ex- ploiting the

  12. Osmotic versus conventional membrane bioreactors integrated with reverse osmosis for water reuse: Biological stability, membrane fouling, and contaminant removal.

    Science.gov (United States)

    Luo, Wenhai; Phan, Hop V; Xie, Ming; Hai, Faisal I; Price, William E; Elimelech, Menachem; Nghiem, Long D

    2017-02-01

    This study systematically compares the performance of osmotic membrane bioreactor - reverse osmosis (OMBR-RO) and conventional membrane bioreactor - reverse osmosis (MBR-RO) for advanced wastewater treatment and water reuse. Both systems achieved effective removal of bulk organic matter and nutrients, and almost complete removal of all 31 trace organic contaminants investigated. They both could produce high quality water suitable for recycling applications. During OMBR-RO operation, salinity build-up in the bioreactor reduced the water flux and negatively impacted the system biological treatment by altering biomass characteristics and microbial community structure. In addition, the elevated salinity also increased soluble microbial products and extracellular polymeric substances in the mixed liquor, which induced fouling of the forward osmosis (FO) membrane. Nevertheless, microbial analysis indicated that salinity stress resulted in the development of halotolerant bacteria, consequently sustaining biodegradation in the OMBR system. By contrast, biological performance was relatively stable throughout conventional MBR-RO operation. Compared to conventional MBR-RO, the FO process effectively prevented foulants from permeating into the draw solution, thereby significantly reducing fouling of the downstream RO membrane in OMBR-RO operation. Accumulation of organic matter, including humic- and protein-like substances, as well as inorganic salts in the MBR effluent resulted in severe RO membrane fouling in conventional MBR-RO operation. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  13. Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

    Science.gov (United States)

    Kunkle, Brian W.; Yoo, Changwon; Roy, Deodutta

    2013-01-01

    In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors. PMID:23737970

  14. Synthetic biology for engineering acetyl coenzyme a metabolism in yeast

    DEFF Research Database (Denmark)

    Nielsen, Jens

    2014-01-01

    The yeast Saccharomyces cerevisiae is a widely used cell factory for the production of fuels, chemicals, and pharmaceuticals. The use of this cell factory for cost-efficient production of novel fuels and chemicals requires high yields and low by-product production. Many industrially interesting...... chemicals are biosynthesized from acetyl coenzyme A (acetyl-CoA), which serves as a central precursor metabolite in yeast. To ensure high yields in production of these chemicals, it is necessary to engineer the central carbon metabolism so that ethanol production is minimized (or eliminated) and acetyl...

  15. Reverse engineering of an affinity-switchable molecular interaction characterized by atomic force microscopy single-molecule force spectroscopy.

    Science.gov (United States)

    Anselmetti, Dario; Bartels, Frank Wilco; Becker, Anke; Decker, Björn; Eckel, Rainer; McIntosh, Matthew; Mattay, Jochen; Plattner, Patrik; Ros, Robert; Schäfer, Christian; Sewald, Norbert

    2008-02-19

    Tunable and switchable interaction between molecules is a key for regulation and control of cellular processes. The translation of the underlying physicochemical principles to synthetic and switchable functional entities and molecules that can mimic the corresponding molecular functions is called reverse molecular engineering. We quantitatively investigated autoinducer-regulated DNA-protein interaction in bacterial gene regulation processes with single atomic force microscopy (AFM) molecule force spectroscopy in vitro, and developed an artificial bistable molecular host-guest system that can be controlled and regulated by external signals (UV light exposure and thermal energy). The intermolecular binding functionality (affinity) and its reproducible and reversible switching has been proven by AFM force spectroscopy at the single-molecule level. This affinity-tunable optomechanical switch will allow novel applications with respect to molecular manipulation, nanoscale rewritable molecular memories, and/or artificial ion channels, which will serve for the controlled transport and release of ions and neutral compounds in the future.

  16. Engineering derivatives from biological systems for advanced aerospace applications

    Science.gov (United States)

    Winfield, Daniel L.; Hering, Dean H.; Cole, David

    1991-01-01

    The present study consisted of a literature survey, a survey of researchers, and a workshop on bionics. These tasks produced an extensive annotated bibliography of bionics research (282 citations), a directory of bionics researchers, and a workshop report on specific bionics research topics applicable to space technology. These deliverables are included as Appendix A, Appendix B, and Section 5.0, respectively. To provide organization to this highly interdisciplinary field and to serve as a guide for interested researchers, we have also prepared a taxonomy or classification of the various subelements of natural engineering systems. Finally, we have synthesized the results of the various components of this study into a discussion of the most promising opportunities for accelerated research, seeking solutions which apply engineering principles from natural systems to advanced aerospace problems. A discussion of opportunities within the areas of materials, structures, sensors, information processing, robotics, autonomous systems, life support systems, and aeronautics is given. Following the conclusions are six discipline summaries that highlight the potential benefits of research in these areas for NASA's space technology programs.

  17. The collective biology of the gene: Towards genetic dynamics engineering

    International Nuclear Information System (INIS)

    Chela-Flores, J.

    1985-11-01

    Chromatin dynamics is studied in terms of coupled vibrations (phonon pairing); this is shown to lead to a collective variable Δ, interpreted as a gene inhibition factor, which behaves as a biological switch turned off, not only by enzymatic action or metabolic energy, but also by means of an external probe:irradiation. We discuss the inactivation of the X chromosome and puffing. The relevance of being able to modulate Δ is emphasized, since it is equivalent to controlling chromatin dynamics without interfering with chromatin structure, unlike in the usual recombinant DNA techniques. (author)

  18. Biotechnology and synthetic biology approaches for metabolic engineering of bioenergy crops.

    Science.gov (United States)

    Shih, Patrick M; Liang, Yan; Loqué, Dominique

    2016-07-01

    The Green Revolution has fuelled an exponential growth in human population since the mid-20th century. Due to population growth, food and energy demands will soon surpass supply capabilities. To overcome these impending problems, significant improvements in genetic engineering will be needed to complement breeding efforts in order to accelerate the improvement of agronomical traits. The new field of plant synthetic biology has emerged in recent years and is expected to support rapid, precise, and robust engineering of plants. In this review, we present recent advances made in the field of plant synthetic biology, specifically in genome editing, transgene expression regulation, and bioenergy crop engineering, with a focus on traits related to lignocellulose, oil, and soluble sugars. Ultimately, progress and innovation in these fields may facilitate the development of beneficial traits in crop plants to meet society's bioenergy needs. © 2016 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  19. Principle and realization of segmenting contour series algorithm in reverse engineering based on X-ray computerized tomography

    International Nuclear Information System (INIS)

    Wang Yanfang; Liu Li; Yan Yonglian; Shan Baoci; Tang Xiaowei

    2007-01-01

    A new algorithm of segmenting contour series of images is presented, which can achieve three dimension reconstruction with parametric recognition in Reverse Engineering based on X-ray CT. First, in order to get the nested relationship between contours, a method of a certain angle ray is used. Second, for realizing the contour location in one slice, another approach is presented to generate the contour tree by scanning the relevant vector only once. Last, a judge algorithm is put forward to accomplish the contour match between slices by adopting the qualitative and quantitative properties. The example shows that this algorithm can segment contour series of CT parts rapidly and precisely. (authors)

  20. Contribution of assimilable organic carbon to biological fouling in seawater reverse osmosis membrane treatment.

    Science.gov (United States)

    Weinrich, Lauren; LeChevallier, Mark; Haas, Charles N

    2016-09-15

    Biological fouling occurs on RO membranes when bacteria and nutrients are present in conditions that are conducive to growth and proliferation of the bacteria. Controlling microbial growth on the membranes is typically limited to biocide application (i.e., disinfectants) in seawater RO plants. However, biological growth and subsequent fouling has not been well-managed. Pretreatment has not been focused on nutrient limitation. This project used a biological assay, the assimilable organic carbon (AOC) test to evaluate pretreatment effects on the nutrient supply. The AOC test provided a useful surrogate measurement for the biodegradability or biofouling potential of RO feed water. Biofouling observed in controlled conditions at the bench- and pilot-scale resulted in statistically significant correlations between AOC and the operational effects caused by biofouling. Membrane fouling rates are observed through operational changes over time such as increased differential pressure between the membrane feed and concentrate locations and decreased permeate flux through the membrane. In full scale plants there were strong correlations when AOC was used as a predictor variable for increased differential pressure (0.28-0.55 bar from September-December 2012) and decreased specific flux (1.40 L per hour/(m(2) · bar)). Increased differential pressure was associated with RO membrane biological fouling when the median AOC was 50 μg/L during pilot testing. Conditions were also evaluated at the bench-scale using a flat sheet RO membrane. In a comparison test using 30 and 1000 μg/L AOC, fouling was detected on more portions of the membrane when AOC was higher. Biofilm and bacterial deposits were apparent from scanning electron microscope imaging and biomass measurements using ATP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Laura R. Jarboe

    2010-01-01

    Full Text Available Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors.

  2. Engineering Algorithms for Finding Patterns in Biological Data

    DEFF Research Database (Denmark)

    Nielsen, Jesper

    2011-01-01

    similarity scores. Association mapping is a technique based on using large amounts of data on Single Nucleotide Polymorphisms (SNPs) to statistically infer associations between segments of DNA and effects in the host. Within the area of association mapping we develop an efficient file format and software...... library, called SNPFile. The file format is able to store both large amounts of SNP data and associated metadata, such as ids and affected-status of samples. Thus the file format can both speed-up SNP data access and simplify data management significantly. On the topic of molecular biological data, we...... analyze data from an experiment on exosome knockout. The exosome is a complex with a role in RNA degradation. We find that knockout of the exosome stabilize hitherto unknown RNA transcripts upstream active transcription start sites. With respect to Hidden Markov Models we develop two fast algorithms. We...

  3. Biomaterials — where biology, physics, chemistry, engineering and medicine meet

    Science.gov (United States)

    Hing, K. A.

    2008-03-01

    The success or failure of an implant material in the body depends on a complex interaction between a synthetic 'foreign body' and the 'host tissue'. These interactions occur at many levels from the sub-microscopic level, where subtle changes in the surface physio-chemistry can substantially alter the nature of the biomaterial-host tissue interface, through the microscopical level (e.g. sensitivity to surface topography) to the macrostructural level (e.g. dependence on scaffold porosity). Thus the factors that control these responses are not only biologically determined but also mechanically, physically and chemically mediated, although identifying where one starts and the other finishes can be difficult. Design of a successful medical device has therefore to call on expertise within a wide range of disciplines. In terms of both investigating the basic science behind the factors which orchestrate a biological response and developing research tools that enable study of these responses. However, a medical device must also meet the economic and practical demands of health care professionals who will ultimately be using it in the clinic. Bone graft substitute materials are used in orthopaedics as an alternative or adjunct to autografting, a practice where the patient 'donates' bone from a healthy site to aid bone repair at a damaged or diseased site. These materials are used in a wide range of procedures from total hip revision to spinal fusion and their evolution over the last 10 years illustrates how an interdisciplinary approach has benefited their development and may lead to further innovation in the future.

  4. 5th European Conference of the International Federation for Medical and Biological Engineering

    CERN Document Server

    European IFMBE MBEC : Cooperation for Effective Healthcare

    2012-01-01

    This volume presents the 5th European Conference of the International Federation for Medical and Biological Engineering (EMBEC),  held in Budapest, 14-18 September, 2011. The scientific discussion on the conference and in this conference proceedings include the following issues: - Signal & Image Processing - ICT - Clinical Engineering and Applications - Biomechanics and Fluid Biomechanics - Biomaterials and Tissue Repair - Innovations and Nanotechnology - Modeling and Simulation - Education and Professional

  5. Biologically improved nanofibrous scaffolds for cardiac tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Bhaarathy, V. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Lee Kong Chian School of Medicine, Nanyang Technological University, 138673 (Singapore); Venugopal, J., E-mail: nnijrv@nus.edu.sg [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Gandhimathi, C. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore); Ponpandian, N.; Mangalaraj, D. [Department of Nanoscience and Technology, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Ramakrishna, S. [Centre for Nanofibers and Nanotechnology, NUSNNI, Faculty of Engineering, National University of Singapore, 117576 (Singapore)

    2014-11-01

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(L-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. - Highlights: • Fabricated nanofibrous scaffolds are porous, beadless and uniform structures. • PLACL/SF/AV nanofibers improve the

  6. Biologically improved nanofibrous scaffolds for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Bhaarathy, V.; Venugopal, J.; Gandhimathi, C.; Ponpandian, N.; Mangalaraj, D.; Ramakrishna, S.

    2014-01-01

    Nanofibrous structure developed by electrospinning technology provides attractive extracellular matrix conditions for the anchorage, migration and differentiation of stem cells, including those responsible for regenerative medicine. Recently, biocomposite nanofibers consisting of two or more polymeric blends are electrospun more tidily in order to obtain scaffolds with desired functional and mechanical properties depending on their applications. The study focuses on one such an attempt of using copolymer Poly(L-lactic acid)-co-poly (ε-caprolactone) (PLACL), silk fibroin (SF) and Aloe Vera (AV) for fabricating biocomposite nanofibrous scaffolds for cardiac tissue engineering. SEM micrographs of fabricated electrospun PLACL, PLACL/SF and PLACL/SF/AV nanofibrous scaffolds are porous, beadless, uniform nanofibers with interconnected pores and obtained fibre diameter in the range of 459 ± 22 nm, 202 ± 12 nm and 188 ± 16 nm respectively. PLACL, PLACL/SF and PLACL/SF/AV electrospun mats obtained at room temperature with an elastic modulus of 14.1 ± 0.7, 9.96 ± 2.5 and 7.0 ± 0.9 MPa respectively. PLACL/SF/AV nanofibers have more desirable properties to act as flexible cell supporting scaffolds compared to PLACL for the repair of myocardial infarction (MI). The PLACL/SF and PLACL/SF/AV nanofibers had a contact angle of 51 ± 12° compared to that of 133 ± 15° of PLACL alone. Cardiac cell proliferation was increased by 21% in PLACL/SF/AV nanofibers compared to PLACL by day 6 and further increased to 42% by day 9. Confocal analysis for cardiac expression proteins myosin and connexin 43 was observed better by day 9 compared to all other nanofibrous scaffolds. The results proved that the fabricated PLACL/SF/AV nanofibrous scaffolds have good potentiality for the regeneration of infarcted myocardium in cardiac tissue engineering. - Highlights: • Fabricated nanofibrous scaffolds are porous, beadless and uniform structures. • PLACL/SF/AV nanofibers improve the

  7. The future of metabolic engineering and synthetic biology: towards a systematic practice.

    Science.gov (United States)

    Yadav, Vikramaditya G; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

    2012-05-01

    Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as 'multivariate modular metabolic engineering' (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Biological responses to acidification reversal in Cumbrian streamwaters - invertebrates and bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Tipping, E.; Bass, J.A.B.; Blackburn, J.H.; Hardie, D.J.; Mallinson, H.E.H.; Simon, B.M.

    2000-07-01

    The stream waters of the upper Duddon catchment, situated in the south-west of the English Lake District, have been acidified as a result of acid deposition. However, there is now strong chemical evidence for recovery, as the acidity of deposition decreases. The present study was carried out in order to investigate possible improvements in biological response. This report describes the results of sampling and analysis, carried out to obtain biological data in 1999 for comparison with data obtained in the 1960s and early 1970s for invertebrates and in the 1980s for bacteria. Macro-invertebrate studies were carried out in five streams which had records from the 1960s and 1970s, and which covered a range of pH (ca. 5 to ca. 7). Significantly more macro-invertebrate taxa were found in all the streams in 1999. The macro-invertebrate diversity was greater in 1999, as judged by the Margalef diversity index. There have been significant increases in the values of a macro-invertebrate based acidification index between the 1960s/1970s and the present, consistent with a decrease in stream water acidity. Species of the bacterium Cytophaga, which participates in the decomposition of plant litter, are absent from streams of low pH. Cytophaga was detected in a stream from which it had previously absent, which is consistent with an increase in pH. Taking the results of the present study together with those of previous ones showing that stream and lake acidity in Cumbria have decreased over the last 20-30 years, it can be concluded that decreases in acid deposition (of S) have led to improvements in water quality, and thereby to positive biological responses. (author)

  9. Effect of engineered environment on microbial community structure in biofilter and biofilm on reverse osmosis membrane

    KAUST Repository

    Jeong, Sanghyun; Cho, Kyungjin; Jeong, Dawoon; Lee, Seockheon; Leiknes, TorOve; Vigneswaran, Saravanamuthu; Bae, Hyokwan

    2017-01-01

    Four dual media filters (DMFs) were operated in a biofiltration mode with different engineered environments (DMF I and II: coagulation with/without acidification and DMF III and IV: without/with chlorination). Designed biofilm enrichment reactors

  10. Enhancing the Biological Relevance of Machine Learning Classifiers for Reverse Vaccinology

    Directory of Open Access Journals (Sweden)

    Ashley I. Heinson

    2017-02-01

    Full Text Available Reverse vaccinology (RV is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML techniques to distinguish bacterial protective antigens (BPAs from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM classifier that could discriminate BPAs (n = 200 from non-BPAs (n = 200 with an area under the curve (AUC of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

  11. Enhancing the Biological Relevance of Machine Learning Classifiers for Reverse Vaccinology

    KAUST Repository

    Heinson, Ashley

    2017-02-01

    Reverse vaccinology (RV) is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML) techniques to distinguish bacterial protective antigens (BPAs) from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM) classifier that could discriminate BPAs (n = 200) from non-BPAs (n = 200) with an area under the curve (AUC) of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

  12. Enhancing the Biological Relevance of Machine Learning Classifiers for Reverse Vaccinology

    KAUST Repository

    Heinson, Ashley; Gunawardana, Yawwani; Moesker, Bastiaan; Hume, Carmen; Vataga, Elena; Hall, Yper; Stylianou, Elena; McShane, Helen; Williams, Ann; Niranjan, Mahesan; Woelk, Christopher

    2017-01-01

    Reverse vaccinology (RV) is a bioinformatics approach that can predict antigens with protective potential from the protein coding genomes of bacterial pathogens for subunit vaccine design. RV has become firmly established following the development of the BEXSERO® vaccine against Neisseria meningitidis serogroup B. RV studies have begun to incorporate machine learning (ML) techniques to distinguish bacterial protective antigens (BPAs) from non-BPAs. This research contributes significantly to the RV field by using permutation analysis to demonstrate that a signal for protective antigens can be curated from published data. Furthermore, the effects of the following on an ML approach to RV were also assessed: nested cross-validation, balancing selection of non-BPAs for subcellular localization, increasing the training data, and incorporating greater numbers of protein annotation tools for feature generation. These enhancements yielded a support vector machine (SVM) classifier that could discriminate BPAs (n = 200) from non-BPAs (n = 200) with an area under the curve (AUC) of 0.787. In addition, hierarchical clustering of BPAs revealed that intracellular BPAs clustered separately from extracellular BPAs. However, no immediate benefit was derived when training SVM classifiers on data sets exclusively containing intra- or extracellular BPAs. In conclusion, this work demonstrates that ML classifiers have great utility in RV approaches and will lead to new subunit vaccines in the future.

  13. Reverse engineering of B-pillar with 3D optical scanning for manufacturing of non-uniform thickness part

    Directory of Open Access Journals (Sweden)

    Islam Md. Tasbirul

    2017-01-01

    Full Text Available This paper presents reverse engineering (RE of a complex automobile structural part, B-pillar. As a major part of the automobile body-in white (BiW, B-pillar has substantial opportunity for weight reduction by introducing variable thickness across its sections. To leverage such potential, an existing B-pillar was reverse engineered with a 3D optical scanner and computer aided design (CAD application. First, digital data (i.e. in meshes of exiting B-pillar was obtained by the scanner, and subsequently, this information was utilized in developing a complete 3D CAD model. CATIA V5 was used in the modeling where some of the essential work benches were “Digitized Shape Editor”, “Quick Surface Reconstruction”, “Wireframe and Surface Design”, “Freestyle”, “Generation Shape Design” and “Part design”. In the final CAD design, five different thicknesses were incorporated successfully in order to get a B-pillar with non-uniform sections. This research opened opportunities for thickness optimization and mold tooling design in real time manufacturing.

  14. Impact of environmental inputs on reverse-engineering approach to network structures.

    Science.gov (United States)

    Wu, Jianhua; Sinfield, James L; Buchanan-Wollaston, Vicky; Feng, Jianfeng

    2009-12-04

    Uncovering complex network structures from a biological system is one of the main topic in system biology. The network structures can be inferred by the dynamical Bayesian network or Granger causality, but neither techniques have seriously taken into account the impact of environmental inputs. With considerations of natural rhythmic dynamics of biological data, we propose a system biology approach to reveal the impact of environmental inputs on network structures. We first represent the environmental inputs by a harmonic oscillator and combine them with Granger causality to identify environmental inputs and then uncover the causal network structures. We also generalize it to multiple harmonic oscillators to represent various exogenous influences. This system approach is extensively tested with toy models and successfully applied to a real biological network of microarray data of the flowering genes of the model plant Arabidopsis Thaliana. The aim is to identify those genes that are directly affected by the presence of the sunlight and uncover the interactive network structures associating with flowering metabolism. We demonstrate that environmental inputs are crucial for correctly inferring network structures. Harmonic causal method is proved to be a powerful technique to detect environment inputs and uncover network structures, especially when the biological data exhibit periodic oscillations.

  15. On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.

    Science.gov (United States)

    Rao, Rohit T; Scherholz, Megerle L; Hartmanshenn, Clara; Bae, Seul-A; Androulakis, Ioannis P

    2017-12-05

    The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

  16. The Future of Metabolic Engineering and Synthetic Biology: Towards a Systematic Practice

    Science.gov (United States)

    Yadav, Vikramaditya G.; De Mey, Marjan; Lim, Chin Giaw; Ajikumar, Parayil Kumaran; Stephanopoulos, Gregory

    2012-01-01

    Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as ‘multivariate modular metabolic engineering’ (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering. PMID:22629571

  17. Can Man Control His Biological Evolution? A Symposium on Genetic Engineering. Genetic Engineering

    Science.gov (United States)

    Ramsey, Paul

    1972-01-01

    Presented are issues related to genetic engineering. Increased knowledge of techniques to manipulate genes are apt to create confusion about moral values in relation to unborn babies and other living organisms on earth. Human beings may use this knowledge to disturb the balance maintained by nature. (PS)

  18. Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology

    DEFF Research Database (Denmark)

    Dvořák, Pavel; Nikel, Pablo Ivan; Damborskýc, Jiří

    2017-01-01

    pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack...... of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow....... In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering...

  19. Genome Engineering and Modification Toward Synthetic Biology for the Production of Antibiotics.

    Science.gov (United States)

    Zou, Xuan; Wang, Lianrong; Li, Zhiqiang; Luo, Jie; Wang, Yunfu; Deng, Zixin; Du, Shiming; Chen, Shi

    2018-01-01

    Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products. Here, we review the progress in the development of these genome editing techniques used to engineer new antibiotics, focusing on three aspects of genome engineering: direct cloning of large genomic fragments, genome engineering of gene clusters, and regulation of gene cluster expression. This review will not only summarize the current uses of genomic engineering techniques for cloning and assembly of antibiotic gene clusters or for altering antibiotic synthetic pathways but will also provide perspectives on the future directions of rebuilding biological systems for the design of novel antibiotics. © 2017 Wiley Periodicals, Inc.

  20. Reverse engineering the structural and acoustic behavior of a stradivari violin

    Science.gov (United States)

    Pyrkosz, Michael

    There is a tremendous amount of mystery that surrounds the instruments of Antonio Stradivari. There have been many studies done in the past, but no one completely understands exactly how he made his instruments, or why they are still considered the best in the world. This project is designed to develop an engineering model of one of Stradivari's violins that will accurately simulate the structural and acoustic behavior of the instrument. It also hopes to shine some light on what makes the instruments of Stradivari unique when compared to other violins. It will focus on geometry and material properties, utilizing several modern engineering tools, including CT scanning, experimental modal analysis, finite element analysis, correlation techniques, and acoustic synthesis.

  1. Metabolic engineering of microorganisms for biofuels production: from bugs to synthetic biology to fuels

    Energy Technology Data Exchange (ETDEWEB)

    Kuk Lee, Sung; Chou, Howard; Ham, Timothy S.; Soon Lee, Taek; Keasling, Jay D.

    2009-12-02

    The ability to generate microorganisms that can produce biofuels similar to petroleum-based transportation fuels would allow the use of existing engines and infrastructure and would save an enormous amount of capital required for replacing the current infrastructure to accommodate biofuels that have properties significantly different from petroleum-based fuels. Several groups have demonstrated the feasibility of manipulating microbes to produce molecules similar to petroleum-derived products, albeit at relatively low productivity (e.g. maximum butanol production is around 20 g/L). For cost-effective production of biofuels, the fuel-producing hosts and pathways must be engineered and optimized. Advances in metabolic engineering and synthetic biology will provide new tools for metabolic engineers to better understand how to rewire the cell in order to create the desired phenotypes for the production of economically viable biofuels.

  2. Directed evolution combined with synthetic biology strategies expedite semi-rational engineering of genes and genomes.

    Science.gov (United States)

    Kang, Zhen; Zhang, Junli; Jin, Peng; Yang, Sen

    2015-01-01

    Owing to our limited understanding of the relationship between sequence and function and the interaction between intracellular pathways and regulatory systems, the rational design of enzyme-coding genes and de novo assembly of a brand-new artificial genome for a desired functionality or phenotype are difficult to achieve. As an alternative approach, directed evolution has been widely used to engineer genomes and enzyme-coding genes. In particular, significant developments toward DNA synthesis, DNA assembly (in vitro or in vivo), recombination-mediated genetic engineering, and high-throughput screening techniques in the field of synthetic biology have been matured and widely adopted, enabling rapid semi-rational genome engineering to generate variants with desired properties. In this commentary, these novel tools and their corresponding applications in the directed evolution of genomes and enzymes are discussed. Moreover, the strategies for genome engineering and rapid in vitro enzyme evolution are also proposed.

  3. File Carving and Malware Identification Algorithms Applied to Firmware Reverse Engineering

    Science.gov (United States)

    2013-03-21

    Internet, and use of common network protocols, enable nuisance hacker attacks. Search engines like SHODAN make searching for Internet-facing SCADA networks... pipeline leak in Bellingham, Washington, to pipeline damage and degraded SCADA software performance [1]. The leak and a subsequent explosion resulted in... FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED The views expressed in this thesis are those of the author and do not reflect the official policy or

  4. Research on external flow field of a car based on reverse engineering

    Science.gov (United States)

    Hu, Shushan; Liu, Ronge

    2018-05-01

    In this paper, the point cloud data of FAW-VOLKSWAGEN car body shape is obtained by three coordinate measuring instrument and laser scanning method. The accurate three dimensional model of the car is obtained using CATIA software reverse modelling technology. The car body is gridded, the calculation field and boundary condition type of the car flow field are determined, and the numerical simulation is carried out in Hyper Mesh software. The pressure cloud diagram, velocity vector diagram, air resistance coefficient and lift coefficient of the car are obtained. The calculation results reflect the aerodynamic characteristics of the car's external flow field. The motion of the separation flow on the surface of the vehicle body is well simulated, and the area where the vortex motion is relatively intense has been determined. The results provide a theoretical basis for improving and optimizing the body shape.

  5. Cognitive science in the era of artificial intelligence: A roadmap for reverse-engineering the infant language-learner.

    Science.gov (United States)

    Dupoux, Emmanuel

    2018-04-01

    Spectacular progress in the information processing sciences (machine learning, wearable sensors) promises to revolutionize the study of cognitive development. Here, we analyse the conditions under which 'reverse engineering' language development, i.e., building an effective system that mimics infant's achievements, can contribute to our scientific understanding of early language development. We argue that, on the computational side, it is important to move from toy problems to the full complexity of the learning situation, and take as input as faithful reconstructions of the sensory signals available to infants as possible. On the data side, accessible but privacy-preserving repositories of home data have to be setup. On the psycholinguistic side, specific tests have to be constructed to benchmark humans and machines at different linguistic levels. We discuss the feasibility of this approach and present an overview of current results. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Effective multiple oral administration of reverse genetics engineered infectious bursal disease virus in mice in the presence of neutralizing antibodies.

    Science.gov (United States)

    Hornyák, Ákos; Lipinski, Kai S; Bakonyi, Tamás; Forgách, Petra; Horváth, Ernő; Farsang, Attila; Hedley, Susan J; Palya, Vilmos; Bakács, Tibor; Kovesdi, Imre

    2015-01-01

    Despite spectacular successes in hepatitis B and C therapies, severe hepatic impairment is still a major treatment problem. The clinically tested infectious bursal disease virus (IBDV) superinfection therapy promises an innovative, interferon-free solution to this great unmet need, provided that a consistent manufacturing process preventing mutations or reversions to virulent strains is obtained. To address safety concerns, a tissue culture adapted IBDV vaccine strain V903/78 was cloned into cDNA plasmids ensuring reproducible production of a reverse engineered virus R903/78. The therapeutic drug candidate was characterized by immunocytochemistry assay, virus particle determination and immunoblot analysis. The biodistribution and potential immunogenicity of the IBDV agent was determined in mice, which is not a natural host of this virus, by quantitative detection of IBDV RNA by a quantitative reverse transcriptase-polymerase chain reaction and virus neutralization test, respectively. Several human cell lines supported IBDV propagation in the absence of visible cytopathic effect. The virus was stable from pH 8 to pH 6 and demonstrated significant resistance to low pH and also proved to be highly resistant to high temperatures. No pathological effects were observed in mice. Single and multiple oral administration of IBDV elicited antibodies with neutralizing activities in vitro. Repeat oral administration of R903/78 was successful despite the presence of neutralizing antibodies. Single oral and intravenous administration indicated that IBDV does not replicate in mammalian liver alleviating some safety related concerns. These data supports the development of an orally delivered anti-hepatitis B virus/ anti-hepatitis C virus viral agent for human use. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Biofuel production in Escherichia coli. The role of metabolic engineering and synthetic biology

    Energy Technology Data Exchange (ETDEWEB)

    Clomburg, James M. [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Gonzalez, Ramon [Rice Univ., Houston, TX (United States). Dept. of Chemical and Biomolecular Engineering; Rice Univ., Houston, TX (United States). Dept. of Bioengineering

    2010-03-15

    The microbial production of biofuels is a promising avenue for the development of viable processes for the generation of fuels from sustainable resources. In order to become cost and energy effective, these processes must utilize organisms that can be optimized to efficiently produce candidate fuels from a variety of feedstocks. Escherichia coli has become a promising host organism for the microbial production of biofuels in part due to the ease at which this organism can be manipulated. Advancements in metabolic engineering and synthetic biology have led to the ability to efficiently engineer E. coli as a biocatalyst for the production of a wide variety of potential biofuels from several biomass constituents. This review focuses on recent efforts devoted to engineering E. coli for the production of biofuels, with emphasis on the key aspects of both the utilization of a variety of substrates as well as the synthesis of several promising biofuels. Strategies for the efficient utilization of carbohydrates, carbohydrate mixtures, and noncarbohydrate carbon sources will be discussed along with engineering efforts for the exploitation of both fermentative and nonfermentative pathways for the production of candidate biofuels such as alcohols and higher carbon biofuels derived from fatty acid and isoprenoid pathways. Continued advancements in metabolic engineering and synthetic biology will help improve not only the titers, yields, and productivities of biofuels discussed herein, but also increase the potential range of compounds that can be produced. (orig.)

  8. Cuckoo Search Algorithm with Lévy Flights for Global-Support Parametric Surface Approximation in Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Andrés Iglesias

    2018-03-01

    Full Text Available This paper concerns several important topics of the Symmetry journal, namely, computer-aided design, computational geometry, computer graphics, visualization, and pattern recognition. We also take advantage of the symmetric structure of the tensor-product surfaces, where the parametric variables u and v play a symmetric role in shape reconstruction. In this paper we address the general problem of global-support parametric surface approximation from clouds of data points for reverse engineering applications. Given a set of measured data points, the approximation is formulated as a nonlinear continuous least-squares optimization problem. Then, a recent metaheuristics called Cuckoo Search Algorithm (CSA is applied to compute all relevant free variables of this minimization problem (namely, the data parameters and the surface poles. The method includes the iterative generation of new solutions by using the Lévy flights to promote the diversity of solutions and prevent stagnation. A critical advantage of this method is its simplicity: the CSA requires only two parameters, many fewer than any other metaheuristic approach, so the parameter tuning becomes a very easy task. The method is also simple to understand and easy to implement. Our approach has been applied to a benchmark of three illustrative sets of noisy data points corresponding to surfaces exhibiting several challenging features. Our experimental results show that the method performs very well even for the cases of noisy and unorganized data points. Therefore, the method can be directly used for real-world applications for reverse engineering without further pre/post-processing. Comparative work with the most classical mathematical techniques for this problem as well as a recent modification of the CSA called Improved CSA (ICSA is also reported. Two nonparametric statistical tests show that our method outperforms the classical mathematical techniques and provides equivalent results to ICSA

  9. Proceedings of the international workshop on engineering design of next step reversed field pinch devices

    International Nuclear Information System (INIS)

    Thomson, D.B.

    1987-11-01

    These Proceedings contain the formal contributed papers, the workshop papers and workshop summaries presented at the International Workshop on Engineering Design of Next Step RFP Devices held at Los Alamos, July 13-17, 1987. Contributed papers were presented at formal sessions on the topics: (1) physics overview (3 papers); (2) general overview (3 papers); (3) front-end (9 papers); (4) computer control and data acquisition (1 paper); (5) magnetics (5 papers); and (6) electrical design (9 papers). Informal topical workshop sessions were held on the topics: (1) RFP physics (9 papers); (2) front-end (7 papers); (3) magnetics (3 papers); and (4) electrical design (1 paper). This volume contains the summaries written by the Chairmen of each of the informal topical workshop sessions. The papers in these Proceedings represent a significant review of the status of the technical base for the engineering design of the next step RFP devices being developed in the US, Europe, and Japan, as of this date

  10. Proceedings of the international workshop on engineering design of next step reversed field pinch devices

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, D.B. (comp.)

    1987-11-01

    These Proceedings contain the formal contributed papers, the workshop papers and workshop summaries presented at the International Workshop on Engineering Design of Next Step RFP Devices held at Los Alamos, July 13-17, 1987. Contributed papers were presented at formal sessions on the topics: (1) physics overview (3 papers); (2) general overview (3 papers); (3) front-end (9 papers); (4) computer control and data acquisition (1 paper); (5) magnetics (5 papers); and (6) electrical design (9 papers). Informal topical workshop sessions were held on the topics: (1) RFP physics (9 papers); (2) front-end (7 papers); (3) magnetics (3 papers); and (4) electrical design (1 paper). This volume contains the summaries written by the Chairmen of each of the informal topical workshop sessions. The papers in these Proceedings represent a significant review of the status of the technical base for the engineering design of the next step RFP devices being developed in the US, Europe, and Japan, as of this date.

  11. Proceedings of Synthetic Biology: Engineering, Evolution and Design (SEED) Conference 2015

    Energy Technology Data Exchange (ETDEWEB)

    Silver, Pamela [Harvard Univ., Cambridge, MA (United States); SEED 2015 Conference Chair; Flach, Evan [American Institute of Chemical Engineers; SEED 2015 Conference Organizer

    2016-10-27

    Synthetic Biology is an emerging discipline that seeks to accelerate the process of engineering biology. As such, the tools are broadly applicable to application areas, including chemicals and biofuels, materials, medicine and agriculture. A characteristic of the field is to look holistically at cellular design, from sensing and genetic circuitry to the manipulation of cellular processes and actuators, to controlling metabolism, to programming multicellular behaviors. Further, the types of cells that are manipulated are broad, from in vitro systems to microbes and fungi to mammalian and plant cells and living animals. Many of the projects in synthetic biology seek to move biochemical functions across organisms. The field is highly interdisciplinary with faculty and students spread across departments that focus on engineering (biological, chemical, electrical, mechanical, civil, computer science) and basic science (biology and systems biology, chemistry, physics). While there have been many one-off workshops and meeting on synthetic biology, the 2014 Synthetic Biology: Engineering, Evolution and Design (SEED) was the first of an annual conference series that serves as a reliable place to pull together the involved disciplines in order to organize and exchange advances in the science and technology in the field. Further, the SEED conferences have a strong focus on industry, with many companies represented and actively participating. A number of these companies have started major efforts in synthetic biology including large companies (e.g., Pfizer, Novartis, Dow, Dupont, BP, Total), smaller companies have recently gone public (e.g., Amyris, Gevo, Intrexon), and many start-ups (e.g., Teslagen, Refactored Materials, Pivot, Genomatica). There are a number of loosely affiliated Synthetic Biology Centers, including ones at MIT, Boston University, UCSD, UCSF, UC-Berkeley, Imperial College, Oxford, and ETH. SEED 2015 will serve as the primary meeting at which international

  12. Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects

    Directory of Open Access Journals (Sweden)

    Chonglong Wang

    2014-09-01

    Full Text Available Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations.

  13. Synthetic biology and metabolic engineering for marine carotenoids: new opportunities and future prospects.

    Science.gov (United States)

    Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

    2014-09-17

    Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations.

  14. Synthetic Biology and Metabolic Engineering for Marine Carotenoids: New Opportunities and Future Prospects

    Science.gov (United States)

    Wang, Chonglong; Kim, Jung-Hun; Kim, Seon-Won

    2014-01-01

    Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations. PMID:25233369

  15. Accuracy of energy measurement and reversible operation of a microcanonical Szilard engine.

    Science.gov (United States)

    Bergli, Joakim

    2014-04-01

    In a recent paper [Vaikuntanathan and Jarzynski, Phys. Rev. E 83, 061120 (2011)], a model was introduced whereby work could be extracted from a thermal bath by measuring the energy of a particle that was thermalized by the bath and manipulating the potential of the particle in the appropriate way, depending on the measurement outcome. If the extracted work is Wextracted and the work Werasure needed to be dissipated in order to erase the measured information in accordance with Landauer's principle, it was shown that Wextracted≤Werasure in accordance with the second law of thermodynamics. Here we extend this work in two directions: First, we discuss how accurately the energy should be measured. By increasing the accuracy one can extract more work, but at the same time one obtains more information that has to be deleted. We discuss what are the appropriate ways of optimizing the balance between the two and find optimal solutions. Second, whenever Wextracted is strictly less than Werasure it means that an irreversible step has been performed. We identify the irreversible step and propose a protocol that will achieve the same transition in a reversible way, increasing Wextracted so that Wextracted=Werasure.

  16. Reverse Engineering the Inflammatory "Clock": From Computational Modeling to Rational Resetting.

    Science.gov (United States)

    Vodovotz, Yoram

    2016-01-01

    Properly-regulated inflammation is central to homeostasis. Traumatic injury, hemorrhagic shock, septic shock, and other injury-related processes such as wound healing are associated with dysregulated inflammation. Like many biological processes, inflammation is a dynamic, complex system whose function, like that of an analog clock, cannot be discerned simply from a laundry list of its parts (data). The advent of multiplexed platforms for gathering biological data, while providing an unprecedented level of detailed information about the inflammatory response, has paradoxically also proven to be overwhelming. This problem is especially acute when the datasets involve time courses, since typical statistical analyses and data-driven modeling are geared towards single time points. Various groups have addressed this problem using dynamic approaches to data-driven and mechanistic computational modeling. These modeling tools can be thought of as the "gears" and "hands" of the "clock," and have led to insights regarding principal drivers, dynamic networks, feedbacks, and regulatory switches that characterize and perhaps regulate the inflammatory response. In parallel, mechanistic computational models have given an abstracted sense of how the inflammatory "clock" works, leading to in silico models of critically ill individuals and populations. Integrating data-driven and mechanistic modeling may point the way to a rational "resetting" of inflammation via model-driven precision medicine.

  17. Delineation and interpretation of gene networks towards their effect in cellular physiology- a reverse engineering approach for the identification of critical molecular players, through the use of ontologies.

    Science.gov (United States)

    Moutselos, K; Maglogiannis, I; Chatziioannou, A

    2010-01-01

    Exploiting ontologies, provides clues regarding the involvement of certain molecular processes in the cellular phenotypic manifestation. However, identifying individual molecular actors (genes, proteins, etc.) for targeted biological validation in a generic, prioritized, fashion, based in objective measures of their effects in the cellular physiology, remains a challenge. In this work, a new meta-analysis algorithm is proposed for the holistic interpretation of the information captured in -omic experiments, that is showcased in a transcriptomic, dynamic, DNA microarray dataset, which examines the effect of mastic oil treatment in Lewis lung carcinoma cells. Through the use of the Gene Ontology this algorithm relates genes to specific cellular pathways and vice versa in order to further reverse engineer the critical role of specific genes, starting from the results of various statistical enrichment analyses. The algorithm is able to discriminate candidate hub-genes, implying critical biochemical cross-talk. Moreover, performance measures of the algorithm are derived, when evaluated with respect to the differential expression gene list of the dataset.

  18. Proceedings of the 8. Mediterranean Conference on Medical and Biological Engineering and Computing (Medicon `98)

    Energy Technology Data Exchange (ETDEWEB)

    Christofides, Stelios; Pattichis, Constantinos; Schizas, Christos; Keravnou-Papailiou, Elpida; Kaplanis, Prodromos; Spyros, Spyrou; Christodoulides, George; Theodoulou, Yiannis [eds.

    1999-12-31

    Medicon `98 is the eighth in the series of regional meetings of the International Federation of Medical and Biological Engineering (IFMBE) in the Mediterranean. The goal of Medicon `98 is to provide updated information on the state of the art on medical and biological engineering and computing. Medicon `98 was held in Lemesos, Cyprus, between 14-17 June, 1998. The full papers of the proceedings were published on CD and consisted of 190 invited and submitted papers. A book of abstracts was also published in paper form and was available to all the participants. Twenty seven papers fall within the scope of INIS and are dealing with Nuclear Medicine,Computerized Tomography, Radiology, Radiotherapy, Magnetic Resonance Imaging and Personnel Dosimetry (eds).

  19. Synthetic constructs in/for the environment: managing the interplay between natural and engineered Biology.

    Science.gov (United States)

    Schmidt, Markus; de Lorenzo, Víctor

    2012-07-16

    The plausible release of deeply engineered or even entirely synthetic/artificial microorganisms raises the issue of their intentional (e.g. bioremediation) or accidental interaction with the Environment. Containment systems designed in the 1980s-1990s for limiting the spread of genetically engineered bacteria and their recombinant traits are still applicable to contemporary Synthetic Biology constructs. Yet, the ease of DNA synthesis and the uncertainty on how non-natural properties and strains could interplay with the existing biological word poses yet again the challenge of designing safe and efficacious firewalls to curtail possible interactions. Such barriers may include xeno-nucleic acids (XNAs) instead of DNA as information-bearing molecules, rewriting the genetic code to make it non-understandable by the existing gene expression machineries, and/or making growth dependent on xenobiotic chemicals. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. Interdisciplinary research and education at the biology-engineering-computer science interface: a perspective.

    Science.gov (United States)

    Tadmor, Brigitta; Tidor, Bruce

    2005-09-01

    Progress in the life sciences, including genome sequencing and high-throughput experimentation, offers an opportunity for understanding biology and medicine from a systems perspective. This 'new view', which complements the more traditional component-based approach, involves the integration of biological research with approaches from engineering disciplines and computer science. The result is more than a new set of technologies. Rather, it promises a fundamental reconceptualization of the life sciences based on the development of quantitative and predictive models to describe crucial processes. To achieve this change, learning communities are being formed at the interface of the life sciences, engineering and computer science. Through these communities, research and education will be integrated across disciplines and the challenges associated with multidisciplinary team-based science will be addressed.

  1. Proceedings of the 8. Mediterranean Conference on Medical and Biological Engineering and Computing (Medicon '98)

    International Nuclear Information System (INIS)

    Christofides, Stelios; Pattichis, Constantinos; Schizas, Christos; Keravnou-Papailiou, Elpida; Kaplanis, Prodromos; Spyros, Spyrou; Christodoulides, George; Theodoulou, Yiannis

    1998-01-01

    Medicon '98 is the eighth in the series of regional meetings of the International Federation of Medical and Biological Engineering (IFMBE) in the Mediterranean. The goal of Medicon '98 is to provide updated information on the state of the art on medical and biological engineering and computing. Medicon '98 was held in Lemesos, Cyprus, between 14-17 June, 1998. The full papers of the proceedings were published on CD and consisted of 190 invited and submitted papers. A book of abstracts was also published in paper form and was available to all the participants. Twenty seven papers fall within the scope of INIS and are dealing with Nuclear Medicine,Computerized Tomography, Radiology, Radiotherapy, Magnetic Resonance Imaging and Personnel Dosimetry (eds)

  2. Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Jahnavi, S [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Saravanan, U [Department of Civil Engineering, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Arthi, N [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Bhuvaneshwar, G S [Department of Engineering Design, Indian Institute of Technology Madras, Chennai, TN 600036 (India); Kumary, T V [Tissue Culture Laboratory, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojappura, Trivandrum, Kerala 695012 (India); Rajan, S [Madras Medical Mission, Institute of Cardio-Vascular Diseases, Mogappair, Chennai, Tamil Nadu 600037 (India); Verma, R S, E-mail: vermars@iitm.ac.in [Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, TN 600036 (India)

    2017-04-01

    Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44{sup +}, αSMA{sup +}, Vimentin{sup +} and CD105{sup −} human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. - Highlights: • We report detailed biological and mechanical investigations of a Bio-Hybrid scaffold. • Optimized polymer thickness yielded desired biological and mechanical properties. • Bio-Hybrid scaffold revealed hVIC proliferation with dense ECM deposition. • Biaxial testing indicated that Bio-Hybrid scaffolds are mechanically stronger than native valves. • Bio-Hybrid scaffold is a promising material for autologous valve tissue engineering.

  3. Dental pulp stem cells. Biology and use for periodontal tissue engineering.

    Science.gov (United States)

    Ashri, Nahid Y; Ajlan, Sumaiah A; Aldahmash, Abdullah M

    2015-12-01

    Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from their relative accessibility and pleasant handling properties. The purpose of this article is to review the biological principles of periodontal tissue engineering, along with the challenges facing the development of a consistent and clinically relevant tissue regeneration platform. This article includes an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors.

  4. Synthetic Biology Approaches to Engineer Probiotics and Members of the Human Microbiota for Biomedical Applications.

    Science.gov (United States)

    Bober, Josef R; Beisel, Chase L; Nair, Nikhil U

    2018-03-12

    An increasing number of studies have strongly correlated the composition of the human microbiota with many human health conditions and, in several cases, have shown that manipulating the microbiota directly affects health. These insights have generated significant interest in engineering indigenous microbiota community members and nonresident probiotic bacteria as biotic diagnostics and therapeutics that can probe and improve human health. In this review, we discuss recent advances in synthetic biology to engineer commensal and probiotic lactic acid bacteria, bifidobacteria, and Bacteroides for these purposes, and we provide our perspective on the future potential of these technologies. 277 Expected final online publication date for the Annual Review of Biomedical Engineering Volume 20 is June 4, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  5. Modularity in developmental biology and artificial organs: a missing concept in tissue engineering.

    Science.gov (United States)

    Lenas, Petros; Luyten, Frank P; Doblare, Manuel; Nicodemou-Lena, Eleni; Lanzara, Andreina Elena

    2011-06-01

    Tissue engineering is reviving itself, adopting the concept of biomimetics of in vivo tissue development. A basic concept of developmental biology is the modularity of the tissue architecture according to which intermediates in tissue development constitute semiautonomous entities. Both engineering and nature have chosen the modular architecture to optimize the product or organism development and evolution. Bioartificial tissues do not have a modular architecture. On the contrary, artificial organs of modular architecture have been already developed in the field of artificial organs. Therefore the conceptual support of tissue engineering by the field of artificial organs becomes critical in its new endeavor of recapitulating in vitro the in vivo tissue development. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  6. Biological variability in biomechanical engineering research: Significance and meta-analysis of current modeling practices.

    Science.gov (United States)

    Cook, Douglas; Julias, Margaret; Nauman, Eric

    2014-04-11

    Biological systems are characterized by high levels of variability, which can affect the results of biomechanical analyses. As a review of this topic, we first surveyed levels of variation in materials relevant to biomechanics, and compared these values to standard engineered materials. As expected, we found significantly higher levels of variation in biological materials. A meta-analysis was then performed based on thorough reviews of 60 research studies from the field of biomechanics to assess the methods and manner in which biological variation is currently handled in our field. The results of our meta-analysis revealed interesting trends in modeling practices, and suggest a need for more biomechanical studies that fully incorporate biological variation in biomechanical models and analyses. Finally, we provide some case study example of how biological variability may provide valuable insights or lead to surprising results. The purpose of this study is to promote the advancement of biomechanics research by encouraging broader treatment of biological variability in biomechanical modeling. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. ARACNe-AP: gene network reverse engineering through adaptive partitioning inference of mutual information.

    Science.gov (United States)

    Lachmann, Alexander; Giorgi, Federico M; Lopez, Gonzalo; Califano, Andrea

    2016-07-15

    The accurate reconstruction of gene regulatory networks from large scale molecular profile datasets represents one of the grand challenges of Systems Biology. The Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) represents one of the most effective tools to accomplish this goal. However, the initial Fixed Bandwidth (FB) implementation is both inefficient and unable to deal with sample sets providing largely uneven coverage of the probability density space. Here, we present a completely new implementation of the algorithm, based on an Adaptive Partitioning strategy (AP) for estimating the Mutual Information. The new AP implementation (ARACNe-AP) achieves a dramatic improvement in computational performance (200× on average) over the previous methodology, while preserving the Mutual Information estimator and the Network inference accuracy of the original algorithm. Given that the previous version of ARACNe is extremely demanding, the new version of the algorithm will allow even researchers with modest computational resources to build complex regulatory networks from hundreds of gene expression profiles. A JAVA cross-platform command line executable of ARACNe, together with all source code and a detailed usage guide are freely available on Sourceforge (http://sourceforge.net/projects/aracne-ap). JAVA version 8 or higher is required. califano@c2b2.columbia.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

  8. Improvement of handle grip using reverse engineering, CAE and Rapid Prototyping

    Directory of Open Access Journals (Sweden)

    Stoklasek Pavel

    2016-01-01

    Full Text Available The overwhelming majority of manual operations is even nowadays performed by using manual hand tools. These tools can be divided into 2 groups – hand tools designed for general use or a single-purpose hand tools for special operations. Tool described in this paper is used in assembling operation in the completion of electric motor. During the design of the existing tools the requirements for a functional part of the tool (lifespan, inability to damage the engine installation were fully considered, demands for ergonomic grip area, however, were not taken into account. Long-term use of incorrectly designed tool causes carpal tunnel syndrome, hand-arm vibration syndrome, diminished sensitivity or tingling in the fingers of workers. These difficulties can be reduced or entirely eliminated due to proper design of the grip of hand tool. Most authors focus on adjusting the grip for optimum ergonomics at individual types of grips (cylindrical, palmar, lateral, etc.. However, as already mentioned, there are tools for specific operations when the working area is limited by space or a specific type of load on the grip is needed. In some cases, it is often necessary to change the type of grip or combine different types of grips. This paper describes the design of an optimal grip of hand tool used for specific operation when assembling motors. Design of prototype mold and production of functional prototypes for ergonomics assessment directly in the workplace were realized. New design of handle should reduce the risk primarily of developing carpal tunnel in long-term use.

  9. Evaluation of a Commercial Tractor Safety Monitoring System Using a Reverse Engineering Procedure.

    Science.gov (United States)

    Casazza, Camilla; Martelli, Roberta; Rondelli, Valda

    2016-10-17

    There is a high rate of work-related deaths in agriculture. In Italy, despite the obligato-ry installation of ROPS, fatal accidents involving tractors represent more than 40% of work-related deaths in agriculture. As death is often due to an overturn that the driver is incapable of predicting, driver assistance devices that can signal critical stability conditions have been studied and marketed to prevent accidents. These devices measure the working parameters of the tractor through sensors and elaborate the values using an algorithm that, taking into account the geometric characteristics of the tractor, pro-vides a risk index based on models elaborated on a theoretical basis. This research aimed to verify one of these stability indexes in the field, using a commercial driver as-sistance device to monitor five tractors on the University of Bologna experimental farm. The setup of the device involved determining the coordinates of the center of gravity of the tractor and the implement mounted on the tractor. The analysis of the stability in-dex, limited to events with a significant risk level, revealed a clear separation into two groups: events with high values of roll or pitch and low speeds, typical of a tractor when working, and events with low values of roll and pitch and high steering angle and forward speed, typical of travel on the road. The equation for calculating the critical speed when turning provided a significant contribution only for events that were typi-cal of travel rather than field work, suggesting a diversified calculation approach ac-cording to the work phase. Copyright© by the American Society of Agricultural Engineers.

  10. Inferring regulatory networks from experimental morphological phenotypes: a computational method reverse-engineers planarian regeneration.

    Directory of Open Access Journals (Sweden)

    Daniel Lobo

    2015-06-01

    Full Text Available Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures, and reveal what external signals will trigger desired changes of large-scale pattern. Despite recent advances in bioinformatics, extracting mechanistic pathway models from experimental morphological data is a key open challenge that has resisted automation. The fundamental difficulty of manually predicting emergent behavior of even simple networks has limited the models invented by human scientists to pathway diagrams that show necessary subunit interactions but do not reveal the dynamics that are sufficient for complex, self-regulating pattern to emerge. To finally bridge the gap between high-resolution genetic data and the ability to understand and control patterning, it is critical to develop computational tools to efficiently extract regulatory pathways from the resultant experimental shape phenotypes. For example, planarian regeneration has been studied for over a century, but despite increasing insight into the pathways that control its stem cells, no constructive, mechanistic model has yet been found by human scientists that explains more than one or two key features of its remarkable ability to regenerate its correct anatomical pattern after drastic perturbations. We present a method to infer the molecular products, topology, and spatial and temporal non-linear dynamics of regulatory networks recapitulating in silico the rich dataset of morphological phenotypes resulting from genetic, surgical, and pharmacological experiments. We demonstrated our approach by inferring complete regulatory networks explaining the outcomes of the main functional regeneration experiments in the planarian literature; By analyzing all the datasets together, our system inferred the first systems-biology comprehensive dynamical model explaining patterning in planarian regeneration. This method

  11. Rabi model as a quantum coherent heat engine: From quantum biology to superconducting circuits

    Science.gov (United States)

    Altintas, Ferdi; Hardal, Ali Ü. C.; Müstecaplıoǧlu, Özgür E.

    2015-02-01

    We propose a multilevel quantum heat engine with a working medium described by a generalized Rabi model which consists of a two-level system coupled to a single-mode bosonic field. The model is constructed to be a continuum limit of a quantum biological description of light-harvesting complexes so that it can amplify quantum coherence by a mechanism which is a quantum analog of classical Huygens clocks. The engine operates in a quantum Otto cycle where the working medium is coupled to classical heat baths in the isochoric processes of the four-stroke cycle, while either the coupling strength or the resonance frequency is changed in the adiabatic stages. We found that such an engine can produce work with an efficiency close to the Carnot bound when it operates at low temperatures and in the ultrastrong-coupling regime. The interplay of the effects of quantum coherence and quantum correlations on the engine performance is discussed in terms of second-order coherence, quantum mutual information, and the logarithmic negativity of entanglement. We point out that the proposed quantum Otto engine can be implemented experimentally with modern circuit quantum electrodynamic systems where flux qubits can be coupled ultrastrongly to superconducting transmission-line resonators.

  12. Reverse engineering of fluid selection for thermodynamic cycles with cubic equations of state, using a compression heat pump as example

    International Nuclear Information System (INIS)

    Roskosch, Dennis; Atakan, Burak

    2015-01-01

    Fluid selection for thermodynamic cycles like refrigeration cycles, heat pumps or organic Rankine cycles remains an actual topic. Generally the search for a working fluid is based on experimental approaches or on a not very systematic trial and error approach, far from being elegant. An alternative method may be a theory based reverse engineering approach, proposed and investigated here: The design process should start with an optimal process and with (abstract) properties of the fluid needed to fit into this optimal process, best described by some general equation of state and the corresponding fluid-describing parameters. These should be analyzed and optimized with respect to the defined model process, which also has to be optimized simultaneously. From this information real fluids can be selected or even synthesized which have fluid defining properties in the optimum regime like critical temperature or ideal gas capacities of heat, allowing to find new working fluids, not considered so far. The number and kind of the fluid-defining parameters is mainly based on the choice of the used EOS (equation of state). The property model used in the present work is based on the cubic Peng–Robinson equation, chosen due to its moderate numerical expense, sufficient accuracy as well as a general availability of the fluid-defining parameters for many compounds. The considered model-process works between the temperature levels of 273.15 and 333.15 K and can be used as heat pump for supplying buildings with heat, typically. The objective functions are the COP (coefficient of performance) and the VHC (volumetric heating capacity) as a function of critical pressure, critical temperature, acentric factor and two coefficients for the temperature-dependent isobaric ideal gas heat capacity. Also, the steam quality at the compressor entrance has to be regarded as a problem variable. The results give clear hints regarding optimal fluid parameters of the analyzed process and deepen

  13. Expanding the chemical palate of cells by combining systems biology and metabolic engineering.

    Science.gov (United States)

    Curran, Kathleen A; Alper, Hal S

    2012-07-01

    The field of Metabolic Engineering has recently undergone a transformation that has led to a rapid expansion of the chemical palate of cells. Now, it is conceivable to produce nearly any organic molecule of interest using a cellular host. Significant advances have been made in the production of biofuels, biopolymers and precursors, pharmaceuticals and nutraceuticals, and commodity and specialty chemicals. Much of this rapid expansion in the field has been, in part, due to synergies and advances in the area of systems biology. Specifically, the availability of functional genomics, metabolomics and transcriptomics data has resulted in the potential to produce a wealth of new products, both natural and non-natural, in cellular factories. The sheer amount and diversity of this data however, means that uncovering and unlocking novel chemistries and insights is a non-obvious exercise. To address this issue, a number of computational tools and experimental approaches have been developed to help expedite the design process to create new cellular factories. This review will highlight many of the systems biology enabling technologies that have reduced the design cycle for engineered hosts, highlight major advances in the expanded diversity of products that can be synthesized, and conclude with future prospects in the field of metabolic engineering. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. BioCarian: search engine for exploratory searches in heterogeneous biological databases.

    Science.gov (United States)

    Zaki, Nazar; Tennakoon, Chandana

    2017-10-02

    There are a large number of biological databases publicly available for scientists in the web. Also, there are many private databases generated in the course of research projects. These databases are in a wide variety of formats. Web standards have evolved in the recent times and semantic web technologies are now available to interconnect diverse and heterogeneous sources of data. Therefore, integration and querying of biological databases can be facilitated by techniques used in semantic web. Heterogeneous databases can be converted into Resource Description Format (RDF) and queried using SPARQL language. Searching for exact queries in these databases is trivial. However, exploratory searches need customized solutions, especially when multiple databases are involved. This process is cumbersome and time consuming for those without a sufficient background in computer science. In this context, a search engine facilitating exploratory searches of databases would be of great help to the scientific community. We present BioCarian, an efficient and user-friendly search engine for performing exploratory searches on biological databases. The search engine is an interface for SPARQL queries over RDF databases. We note that many of the databases can be converted to tabular form. We first convert the tabular databases to RDF. The search engine provides a graphical interface based on facets to explore the converted databases. The facet interface is more advanced than conventional facets. It allows complex queries to be constructed, and have additional features like ranking of facet values based on several criteria, visually indicating the relevance of a facet value and presenting the most important facet values when a large number of choices are available. For the advanced users, SPARQL queries can be run directly on the databases. Using this feature, users will be able to incorporate federated searches of SPARQL endpoints. We used the search engine to do an exploratory search

  15. Biological and mechanical evaluation of a Bio-Hybrid scaffold for autologous valve tissue engineering.

    Science.gov (United States)

    Jahnavi, S; Saravanan, U; Arthi, N; Bhuvaneshwar, G S; Kumary, T V; Rajan, S; Verma, R S

    2017-04-01

    Major challenge in heart valve tissue engineering for paediatric patients is the development of an autologous valve with regenerative capacity. Hybrid tissue engineering approach is recently gaining popularity to design scaffolds with desired biological and mechanical properties that can remodel post implantation. In this study, we fabricated aligned nanofibrous Bio-Hybrid scaffold made of decellularized bovine pericardium: polycaprolactone-chitosan with optimized polymer thickness to yield the desired biological and mechanical properties. CD44 + , αSMA + , Vimentin + and CD105 - human valve interstitial cells were isolated and seeded on these Bio-Hybrid scaffolds. Subsequent biological evaluation revealed interstitial cell proliferation with dense extra cellular matrix deposition that indicated the viability for growth and proliferation of seeded cells on the scaffolds. Uniaxial mechanical tests along axial direction showed that the Bio-Hybrid scaffolds has at least 20 times the strength of the native valves and its stiffness is nearly 3 times more than that of native valves. Biaxial and uniaxial mechanical studies on valve interstitial cells cultured Bio-Hybrid scaffolds revealed that the response along the axial and circumferential direction was different, similar to native valves. Overall, our findings suggest that Bio-Hybrid scaffold is a promising material for future development of regenerative heart valve constructs in children. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Reverse Engineering Tone-Deafness: Disrupting Pitch-Matching by Creating Temporary Dysfunctions in the Auditory-Motor Network

    Directory of Open Access Journals (Sweden)

    Anja Hohmann

    2018-01-01

    Full Text Available Perceiving and producing vocal sounds are important functions of the auditory-motor system and are fundamental to communication. Prior studies have identified a network of brain regions involved in pitch production, specifically pitch matching. Here we reverse engineer the function of the auditory perception-production network by targeting specific cortical regions (e.g., right and left posterior superior temporal (pSTG and posterior inferior frontal gyri (pIFG with cathodal transcranial direct current stimulation (tDCS—commonly found to decrease excitability in the underlying cortical region—allowing us to causally test the role of particular nodes in this network. Performance on a pitch-matching task was determined before and after 20 min of cathodal stimulation. Acoustic analyses of pitch productions showed impaired accuracy after cathodal stimulation to the left pIFG and the right pSTG in comparison to sham stimulation. Both regions share particular roles in the feedback and feedforward motor control of pitched vocal production with a differential hemispheric dominance.

  17. Gas engine driven reversible heat pumps: Innovative design. Realizzazione di una pompa di calore reversibile azionata da motore a gas

    Energy Technology Data Exchange (ETDEWEB)

    Canci, F.; Zecchin, M.

    1992-01-01

    This paper describes the development of a series of gas engine driven air-water compression heat pumps designed for reversible summer-winter operation. The development work was carried out within the framework of a joint venture combing the efforts of the Italian Gas Society, Natural Gas of Barcellona and Climaveneta of Vicenza (Italy), who acted as the heat pump constructor. The main objective of this venture was to develop a series of machines that would be suitable for the contemporaneous summer air conditioning and winter space heating of medium-sized buildings. The designs were optimized to allow cost and energy savings with respect to conventional equipment. The useful cooling power range of the innovative heat pump systems goes from 100 to 250 kW thus giving them the flexibility not yet afforded by conventional equipment currently sold on international markets. In addition to pointing out the new heat pumps' main design and performance features, this paper suggests some feasible applications.

  18. HiDi: an efficient reverse engineering schema for large-scale dynamic regulatory network reconstruction using adaptive differentiation.

    Science.gov (United States)

    Deng, Yue; Zenil, Hector; Tegnér, Jesper; Kiani, Narsis A

    2017-12-15

    The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes. The Matlab code of the HiDi implementation is available at: www.complexitycalculator.com/HiDiScript.zip. hzenilc@gmail.com or narsis.kiani@ki.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  19. Reverse Engineering Applied to Red Human Hair Pheomelanin Reveals Redox-Buffering as a Pro-Oxidant Mechanism

    Science.gov (United States)

    Kim, Eunkyoung; Panzella, Lucia; Micillo, Raffaella; Bentley, William E.; Napolitano, Alessandra; Payne, Gregory F.

    2015-01-01

    Pheomelanin has been implicated in the increased susceptibility to UV-induced melanoma for people with light skin and red hair. Recent studies identified a UV-independent pathway to melanoma carcinogenesis and implicated pheomelanin’s pro-oxidant properties that act through the generation of reactive oxygen species and/or the depletion of cellular antioxidants. Here, we applied an electrochemically-based reverse engineering methodology to compare the redox properties of human hair pheomelanin with model synthetic pigments and natural eumelanin. This methodology exposes the insoluble melanin samples to complex potential (voltage) inputs and measures output response characteristics to assess redox activities. The results demonstrate that both eumelanin and pheomelanin are redox-active, they can rapidly (sec-min) and repeatedly redox-cycle between oxidized and reduced states, and pheomelanin possesses a more oxidative redox potential. This study suggests that pheomelanin’s redox-based pro-oxidant activity may contribute to sustaining a chronic oxidative stress condition through a redox-buffering mechanism. PMID:26669666

  20. HiDi: an efficient reverse engineering schema for large-scale dynamic regulatory network reconstruction using adaptive differentiation

    KAUST Repository

    Deng, Yue

    2017-08-05

    Motivation: The use of differential equations (ODE) is one of the most promising approaches to network inference. The success of ODE-based approaches has, however, been limited, due to the difficulty in estimating parameters and by their lack of scalability. Here, we introduce a novel method and pipeline to reverse engineer gene regulatory networks from gene expression of time series and perturbation data based upon an improvement on the calculation scheme of the derivatives and a pre-filtration step to reduce the number of possible links. The method introduces a linear differential equation model with adaptive numerical differentiation that is scalable to extremely large regulatory networks. Results: We demonstrate the ability of this method to outperform current state-of-the-art methods applied to experimental and synthetic data using test data from the DREAM4 and DREAM5 challenges. Our method displays greater accuracy and scalability. We benchmark the performance of the pipeline with respect to dataset size and levels of noise. We show that the computation time is linear over various network sizes.

  1. Combining selected immunomodulatory Propionibacterium freudenreichii and Lactobacillus delbrueckii strains: Reverse engineering development of an anti-inflammatory cheese.

    Science.gov (United States)

    Plé, Coline; Breton, Jérôme; Richoux, Romain; Nurdin, Marine; Deutsch, Stéphanie-Marie; Falentin, Hélène; Hervé, Christophe; Chuat, Victoria; Lemée, Riwanon; Maguin, Emmanuelle; Jan, Gwénaël; Van de Guchte, Maarten; Foligné, Benoit

    2016-04-01

    Inflammatory bowel disease (IBD) constitutes a growing public health concern in western countries. Bacteria with anti-inflammatory properties are lacking in the dysbiosis accompanying IBD. Selected strains of probiotic bacteria with anti-inflammatory properties accordingly alleviate symptoms and enhance treatment of ulcerative colitis in clinical trials. Such properties are also found in selected strains of dairy starters such as Propionibacterium freudenreichii and Lactobacillus delbrueckii (Ld). We thus investigated the possibility to develop a fermented dairy product, combining both starter and probiotic abilities of both lactic acid and propionic acid bacteria, designed to extend remissions in IBD patients. We developed a single-strain Ld-fermented milk and a two-strain P. freudenreichii and Ld-fermented experimental pressed cheese using strains previously selected for their anti-inflammatory properties. Consumption of these experimental fermented dairy products protected mice against trinitrobenzenesulfonic acid induced colitis, alleviating severity of symptoms, modulating local and systemic inflammation, as well as colonic oxidative stress and epithelial cell damages. As a control, the corresponding sterile dairy matrix failed to afford such protection. This work reveals the probiotic potential of this bacterial mixture, in the context of fermented dairy products. It opens new perspectives for the reverse engineering development of anti-inflammatory fermented foods designed for target populations with IBD, and has provided evidences leading to an ongoing pilot clinical study in ulcerative colitis patients. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals.

    Science.gov (United States)

    Jullesson, David; David, Florian; Pfleger, Brian; Nielsen, Jens

    2015-11-15

    Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine chemicals that have reached the market, key metabolic engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Impact of synthetic biology and metabolic engineering on industrial production of fine chemicals

    DEFF Research Database (Denmark)

    Jullesson, David; David, Florian; Pfleger, Brian

    2015-01-01

    Industrial bio-processes for fine chemical production are increasingly relying on cell factories developed through metabolic engineering and synthetic biology. The use of high throughput techniques and automation for the design of cell factories, and especially platform strains, has played...... chemicals that have reached the market, key metabolic engineering tools that have allowed this to happen and some of the companies that are currently utilizing these technologies for developing industrial production processes....... an important role in the transition from laboratory research to industrial production. Model organisms such as Saccharomyces cerevisiae and Escherichia coli remain widely used host strains for industrial production due to their robust and desirable traits. This review describes some of the bio-based fine...

  4. Recoding aminoacyl-tRNA synthetases for synthetic biology by rational protein-RNA engineering.

    Science.gov (United States)

    Hadd, Andrew; Perona, John J

    2014-12-19

    We have taken a rational approach to redesigning the amino acid binding and aminoacyl-tRNA pairing specificities of bacterial glutaminyl-tRNA synthetase. The four-stage engineering incorporates generalizable design principles and improves the pairing efficiency of noncognate glutamate with tRNA(Gln) by over 10(5)-fold compared to the wild-type enzyme. Better optimized designs of the protein-RNA complex include substantial reengineering of the globular core region of the tRNA, demonstrating a role for specific tRNA nucleotides in specifying the identity of the genetically encoded amino acid. Principles emerging from this engineering effort open new prospects for combining rational and genetic selection approaches to design novel aminoacyl-tRNA synthetases that ligate noncanonical amino acids onto tRNAs. This will facilitate reconstruction of the cellular translation apparatus for applications in synthetic biology.

  5. Enzyme and metabolic engineering for the production of novel biopolymers: crossover of biological and chemical processes.

    Science.gov (United States)

    Matsumoto, Ken'ichiro; Taguchi, Seiichi

    2013-12-01

    The development of synthetic biology has transformed microbes into useful factories for producing valuable polymers and/or their precursors from renewable biomass. Recent progress at the interface of chemistry and biology has enabled the production of a variety of new biopolymers with properties that substantially differ from their petroleum-derived counterparts. This review touches on recent trials and achievements in the field of biopolymer synthesis, including chemo-enzymatically synthesized aliphatic polyesters, wholly biosynthesized lactate-based polyesters, polyhydroxyalkanoates and other unusual bacterially synthesized polyesters. The expanding diversities in structure and the material properties of biopolymers are key for exploring practical applications. The enzyme and metabolic engineering approaches toward this goal are discussed by shedding light on the successful case studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Development and evaluation of a digital dental modeling method based on grating projection and reverse engineering software.

    Science.gov (United States)

    Zhou, Qin; Wang, Zhenzhen; Chen, Jun; Song, Jun; Chen, Lu; Lu, Yi

    2016-01-01

    For reasons of convenience and economy, attempts have been made to transform traditional dental gypsum casts into 3-dimensional (3D) digital casts. Different scanning devices have been developed to generate digital casts; however, each has its own limitations and disadvantages. The purpose of this study was to develop an advanced method for the 3D reproduction of dental casts by using a high-speed grating projection system and noncontact reverse engineering (RE) software and to evaluate the accuracy of the method. The methods consisted of 3 main steps: the scanning and acquisition of 3D dental cast data with a high-resolution grating projection system, the reconstruction and measurement of digital casts with RE software, and the evaluation of the accuracy of this method using 20 dental gypsum casts. The common anatomic landmarks were measured directly on the gypsum casts with a Vernier caliper and on the 3D digital casts with the Geomagic software measurement tool. Data were statistically assessed with the t test. The grating projection system had a rapid scanning speed, and smooth 3D dental casts were obtained. The mean differences between the gypsum and 3D measurements were approximately 0.05 mm, and no statistically significant differences were found between the 2 methods (P>.05), except for the measurements of the incisor tooth width and maxillary arch length. A method for the 3D reconstruction of dental casts was developed by using a grating projection system and RE software. The accuracy of the casts generated using the grating projection system was comparable with that of the gypsum casts. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  7. Use of single-representative reverse-engineered surface-models for RSA does not affect measurement accuracy and precision.

    Science.gov (United States)

    Seehaus, Frank; Schwarze, Michael; Flörkemeier, Thilo; von Lewinski, Gabriela; Kaptein, Bart L; Jakubowitz, Eike; Hurschler, Christof

    2016-05-01

    Implant migration can be accurately quantified by model-based Roentgen stereophotogrammetric analysis (RSA), using an implant surface model to locate the implant relative to the bone. In a clinical situation, a single reverse engineering (RE) model for each implant type and size is used. It is unclear to what extent the accuracy and precision of migration measurement is affected by implant manufacturing variability unaccounted for by a single representative model. Individual RE models were generated for five short-stem hip implants of the same type and size. Two phantom analyses and one clinical analysis were performed: "Accuracy-matched models": one stem was assessed, and the results from the original RE model were compared with randomly selected models. "Accuracy-random model": each of the five stems was assessed and analyzed using one randomly selected RE model. "Precision-clinical setting": implant migration was calculated for eight patients, and all five available RE models were applied to each case. For the two phantom experiments, the 95%CI of the bias ranged from -0.28 mm to 0.30 mm for translation and -2.3° to 2.5° for rotation. In the clinical setting, precision is less than 0.5 mm and 1.2° for translation and rotation, respectively, except for rotations about the proximodistal axis (RSA can be achieved and are not biased by using a single representative RE model. At least for implants similar in shape to the investigated short-stem, individual models are not necessary. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:903-910, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  8. A design concept of parallel elasticity extracted from biological muscles for engineered actuators.

    Science.gov (United States)

    Chen, Jie; Jin, Hongzhe; Iida, Fumiya; Zhao, Jie

    2016-08-23

    Series elastic actuation that takes inspiration from biological muscle-tendon units has been extensively studied and used to address the challenges (e.g. energy efficiency, robustness) existing in purely stiff robots. However, there also exists another form of passive property in biological actuation, parallel elasticity within muscles themselves, and our knowledge of it is limited: for example, there is still no general design strategy for the elasticity profile. When we look at nature, on the other hand, there seems a universal agreement in biological systems: experimental evidence has suggested that a concave-upward elasticity behaviour is exhibited within the muscles of animals. Seeking to draw possible design clues for elasticity in parallel with actuators, we use a simplified joint model to investigate the mechanisms behind this biologically universal preference of muscles. Actuation of the model is identified from general biological joints and further reduced with a specific focus on muscle elasticity aspects, for the sake of easy implementation. By examining various elasticity scenarios, one without elasticity and three with elasticity of different profiles, we find that parallel elasticity generally exerts contradictory influences on energy efficiency and disturbance rejection, due to the mechanical impedance shift thus caused. The trade-off analysis between them also reveals that concave parallel elasticity is able to achieve a more advantageous balance than linear and convex ones. It is expected that the results could contribute to our further understanding of muscle elasticity and provide a theoretical guideline on how to properly design parallel elasticity behaviours for engineering systems such as artificial actuators and robotic joints.

  9. Teaching Synthetic Biology, Bioinformatics and Engineering to Undergraduates: The Interdisciplinary Build-a-Genome Course

    Science.gov (United States)

    Dymond, Jessica S.; Scheifele, Lisa Z.; Richardson, Sarah; Lee, Pablo; Chandrasegaran, Srinivasan; Bader, Joel S.; Boeke, Jef D.

    2009-01-01

    A major challenge in undergraduate life science curricula is the continual evaluation and development of courses that reflect the constantly shifting face of contemporary biological research. Synthetic biology offers an excellent framework within which students may participate in cutting-edge interdisciplinary research and is therefore an attractive addition to the undergraduate biology curriculum. This new discipline offers the promise of a deeper understanding of gene function, gene order, and chromosome structure through the de novo synthesis of genetic information, much as synthetic approaches informed organic chemistry. While considerable progress has been achieved in the synthesis of entire viral and prokaryotic genomes, fabrication of eukaryotic genomes requires synthesis on a scale that is orders of magnitude higher. These high-throughput but labor-intensive projects serve as an ideal way to introduce undergraduates to hands-on synthetic biology research. We are pursuing synthesis of Saccharomyces cerevisiae chromosomes in an undergraduate laboratory setting, the Build-a-Genome course, thereby exposing students to the engineering of biology on a genomewide scale while focusing on a limited region of the genome. A synthetic chromosome III sequence was designed, ordered from commercial suppliers in the form of oligonucleotides, and subsequently assembled by students into ∼750-bp fragments. Once trained in assembly of such DNA “building blocks” by PCR, the students accomplish high-yield gene synthesis, becoming not only technically proficient but also constructively critical and capable of adapting their protocols as independent researchers. Regular “lab meeting” sessions help prepare them for future roles in laboratory science. PMID:19015540

  10. Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology.

    Science.gov (United States)

    Dvořák, Pavel; Nikel, Pablo I; Damborský, Jiří; de Lorenzo, Víctor

    2017-11-15

    Elimination or mitigation of the toxic effects of chemical waste released to the environment by industrial and urban activities relies largely on the catalytic activities of microorganisms-specifically bacteria. Given their capacity to evolve rapidly, they have the biochemical power to tackle a large number of molecules mobilized from their geological repositories through human action (e.g., hydrocarbons, heavy metals) or generated through chemical synthesis (e.g., xenobiotic compounds). Whereas naturally occurring microbes already have considerable ability to remove many environmental pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow revisiting the same environmental pollution challenges through fresh and far more powerful approaches. The focus on contaminated sites and chemicals has been broadened by the phenomenal problems of anthropogenic emissions of greenhouse gases and the accumulation of plastic waste on a global scale. In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering workflow. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Informing via Research: Methods, Challenges and Success when Using a Multi-Disciplinary Team and Reverse Engineering Analysis Processes to Answer a 200 Year Old Question

    Directory of Open Access Journals (Sweden)

    Melinda H. Connor

    2014-10-01

    Full Text Available The goal of this study was to develop the foundation for the creation of a 21st century spiritual which could be used to mitigate the effects of stress and violence. Using a multi-disciplinary team and basing the work in the music of the antebellum Negro Spiritual (a group of 6000 works, reverse engineering, extensive use of engineering principles and utilization of existing databases was done to aid in the analysis of the neurological and physiological impact of the musical form and development of an applicable theory.

  12. Genetically engineered mouse models of craniopharyngioma: an opportunity for therapy development and understanding of tumor biology.

    Science.gov (United States)

    Apps, John Richard; Martinez-Barbera, Juan Pedro

    2017-05-01

    Adamantinomatous craniopharyngioma (ACP) is the commonest tumor of the sellar region in childhood. Two genetically engineered mouse models have been developed and are giving valuable insights into ACP biology. These models have identified novel pathways activated in tumors, revealed an important function of paracrine signalling and extended conventional theories about the role of organ-specific stem cells in tumorigenesis. In this review, we summarize these mouse models, what has been learnt, their limitations and open questions for future research. We then discussed how these mouse models may be used to test novel therapeutics against potentially targetable pathways recently identified in human ACP. © 2017 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

  13. Biological performance of titania containing phosphate-based glasses for bone tissue engineering applications

    International Nuclear Information System (INIS)

    Abou Neel, Ensanya Ali; Chrzanowski, Wojciech; Knowles, Jonathan Campbell

    2014-01-01

    The interplay between glass chemistry, structure, degradation kinetics, and biological activity provides flexibility for the development of scaffolds with highly specific cellular response. The aim of this study was therefore to investigate the role of titania inclusion into the phosphate-based glass on its ability to stimulate osteoblast-like human osteosarcoma (HOS) cells to adhere, proliferate and differentiate. In depth morphological and biochemical characterisation was performed on HOS cells cultured on the surface of glass discs. Cell proliferation was also studied in the presence of the glass extract. Cell differentiation, through osteoblast phenotype genes, alkaline phosphatase (ALP) activity and osteocalcin production, was carried out using normal or osteogenic media. Both Thermanox® and titania free glass were used as controls. The data demonstrated that titania inclusion provides desired cytocompatible surface that supported initial cell attachment, sustained viability, and increased cell proliferation similar or significantly higher than Thermanox®. The modified glasses regulated osteoblastic cell differentiation as detected by osteoblast phenotype gene transcription and upregulated ALP and osteocalcin expression. Using osteogenic media had no significant effect on ALP activity and osteocalcin expression. Therefore, titania modified phosphate glasses may have future use as bone tissue engineering scaffolds. - Highlights: • This study investigated the role of titania on the biological response of phosphate glasses. • Incorporation of titania improved HOS cell attachment, viability and proliferation. • Titania modified glasses regulated osteoblastic cell differentiation. • Using osteogenic media had no significant effect on cell differentiation. • Titania modified glasses may have future use as bone tissue engineering scaffolds

  14. A new class of potential chloroquine-resistance reversal agents for Plasmodia: syntheses and biological evaluation of 1-(3'-diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines.

    Science.gov (United States)

    Batra, S; Srivastava, P; Roy, K; Pandey, V C; Bhaduri, A P

    2000-09-07

    1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the results are presented. The possible mode of action of the compounds of this series is by inhibition of the enzyme heme oxygenase, thereby increasing the levels of heme and hemozoin, which are lethal to the parasite.

  15. Biologically inspired robotic inspectors: the engineering reality and future outlook (Keynote address)

    Science.gov (United States)

    Bar-Cohen, Yoseph

    2005-04-01

    Human errors have long been recognized as a major factor in the reliability of nondestructive evaluation results. To minimize such errors, there is an increasing reliance on automatic inspection tools that allow faster and consistent tests. Crawlers and various manipulation devices are commonly used to perform variety of inspection procedures that include C-scan with contour following capability to rapidly inspect complex structures. The emergence of robots has been the result of the need to deal with parts that are too complex to handle by a simple automatic system. Economical factors are continuing to hamper the wide use of robotics for inspection applications however technology advances are increasingly changing this paradigm. Autonomous robots, which may look like human, can potentially address the need to inspect structures with configuration that are not predetermined. The operation of such robots that mimic biology may take place at harsh or hazardous environments that are too dangerous for human presence. Biomimetic technologies such as artificial intelligence, artificial muscles, artificial vision and numerous others are increasingly becoming common engineering tools. Inspired by science fiction, making biomimetic robots is increasingly becoming an engineering reality and in this paper the state-of-the-art will be reviewed and the outlook for the future will be discussed.

  16. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

    Science.gov (United States)

    Tien, Shin-Ming; Hsu, Chih-Yuan; Chen, Bor-Sen

    2016-01-01

    Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

  17. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

    Directory of Open Access Journals (Sweden)

    Shin-Ming Tien

    Full Text Available Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

  18. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

    Science.gov (United States)

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

    2015-07-06

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

  19. Translational systems biology: introduction of an engineering approach to the pathophysiology of the burn patient.

    Science.gov (United States)

    An, Gary; Faeder, James; Vodovotz, Yoram

    2008-01-01

    The pathophysiology of the burn patient manifests the full spectrum of the complexity of the inflammatory response. In the acute phase, inflammation may have negative effects via capillary leak, the propagation of inhalation injury, and development of multiple organ failure. Attempts to mediate these processes remain a central subject of burn care research. Conversely, inflammation is a necessary prologue and component in the later stage processes of wound healing. Despite the volume of information concerning the cellular and molecular processes involved in inflammation, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective clinical therapeutic regimens. Translational systems biology (TSB) is the application of dynamic mathematical modeling and certain engineering principles to biological systems to integrate mechanism with phenomenon and, importantly, to revise clinical practice. This study will review the existing applications of TSB in the areas of inflammation and wound healing, relate them to specific areas of interest to the burn community, and present an integrated framework that links TSB with traditional burn research.

  20. Cuttlefish bone scaffold for tissue engineering: a novel hydrothermal transformation, chemical-physical, and biological characterization.

    Science.gov (United States)

    Battistella, Elisa; Mele, Silvia; Foltran, Ismaela; Lesci, Isidoro Giorgio; Roveri, Norberto; Sabatino, Piera; Rimondini, Lia

    2012-09-27

    Natural resources are receiving growing interest because of their possible conversion from a cheap and easily available material into a biomedical product. Cuttlefish bone from Sepia Officinalis was investigated in order to obtain an hydroxyapatite porous scaffold using hydrothermal transformation. Complete conversion of the previous calcium carbonate (aragonite) phase into a calcium phosphate (hydroxyapatite) phase was performed with an hydrothermal transformation at 200 °C (~ 15 atm), for four hours, with an aqueous solution of KH2PO4 in order to set the molar ratio Ca/P = 10/6 in a reactor (Parr 4382). The complete conversion was then analyzed by TGA, ATR-FTIR, x-ray diffraction, and SEM. Moreover, the material was biologically investigated with MC3T3-E1 in static cultures, using both osteogenic and maintenance media. The expression of osteogenic markers as ALP and osteocalcin and the cell proliferation were investigated. Cuttlefish bone has been successfully transformed from calcium carbonate into calcium phosphate. Biological characterization revealed that osteogenic markers are expressed using both osteogenic and maintenance conditions. Cell proliferation is influenced by the static culture condition used for this three-dimensional scaffold. The new scaffold composed by hydroxyapatite and derived for a natural source presents good biocompatibility and can be used for further investigations using dynamic cultures in order to improve cell proliferation and differentiation for bone tissue engineering.

  1. Nanodimensional and Nanocrystalline Apatites and Other Calcium Orthophosphates in Biomedical Engineering, Biology and Medicine

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2009-11-01

    Full Text Available Recent developments in biomineralization have already demonstrated that nanosized particles play an important role in the formation of hard tissues of animals. Namely, the basic inorganic building blocks of bones and teeth of mammals are nanodimensional and nanocrystalline calcium orthophosphates (in the form of apatites of a biological origin. In mammals, tens to hundreds nanocrystals of a biological apatite were found to be combined into self-assembled structures under the control of various bioorganic matrixes. In addition, the structures of both dental enamel and bones could be mimicked by an oriented aggregation of nanosized calcium orthophosphates, determined by the biomolecules. The application and prospective use of nanodimensional and nanocrystalline calcium orthophosphates for a clinical repair of damaged bones and teeth are also known. For example, a greater viability and a better proliferation of various types of cells were detected on smaller crystals of calcium orthophosphates. Thus, the nanodimensional and nanocrystalline forms of calcium orthophosphates have a great potential to revolutionize the field of hard tissue engineering starting from bone repair and augmentation to the controlled drug delivery devices. This paper reviews current state of knowledge and recent developments of this subject starting from the synthesis and characterization to biomedical and clinical applications. More to the point, this review provides possible directions of future research and development.

  2. Enzyme engineering through evolution: thermostable recombinant group II intron reverse transcriptases provide new tools for RNA research and biotechnology.

    Science.gov (United States)

    Collins, Kathleen; Nilsen, Timothy W

    2013-08-01

    Current investigation of RNA transcriptomes relies heavily on the use of retroviral reverse transcriptases. It is well known that these enzymes have many limitations because of their intrinsic properties. This commentary highlights the recent biochemical characterization of a new family of reverse transcriptases, those encoded by group II intron retrohoming elements. The novel properties of these enzymes endow them with the potential to revolutionize how we approach RNA analyses.

  3. Identification of cysteine proteases and screening of cysteine protease inhibitors in biological samples by a two-dimensional gel system of zymography and reverse zymography.

    Science.gov (United States)

    Saitoh, Eiichi; Yamamoto, Shinya; Okamoto, Eishiro; Hayakawa, Yoshimi; Hoshino, Takashi; Sato, Ritsuko; Isemura, Satoko; Ohtsubo, Sadami; Taniguchi, Masayuki

    2007-11-18

    We have developed a two-dimensional (2D-) gel system of zymography and reverse zymography for the detection and characterization of proteases and protease inhibitors. Isoelectric focusing (IEF) agarose gels with pH gradients were employed for separation in the first-dimension and sodium dodecyl sulfate (SDS)-polyacrylamide gel copolymerized with gelatin used for the second dimension. Proteases and protease inhibitors separated by IEF gel were applied on the second gel without trichloroacetic acid (TCA) fixation. Protease activity in the 2D-gel was visualized as transparent spots where gelatin substrate was digested after commassie brilliant blue (CBB) staining. Some of the transparent spots from the skin mucus extract of rainbow trout were determined to be a cysteine protease through use of E-64 or CA-074. In the reverse zymography technique, the gel was incubated with papain solution at 37 degrees C for 18 h. Cysteine protease inhibitors from broad bean seeds were detected as clear blue spots after CBB staining. The amino (N-) terminal sequences of four papain inhibitor spots thus detected were demonstrated to be identical to that of favin beta chain, a broad bean lectin. Taken together, our system can be considered to be an efficient technique for discovering and characterizing new proteases and protease inhibitors in biological samples. This is the first report describing a 2D-gel system of zymography and reverse zymography.

  4. Proceedings of the Joint Conference of Australasian College of Physical Scientists and Engineers in Medicine and IEAust College of Biomedical Engineers; Asia/Pacific Region of the IEEE Engineering in Medicine and Biology Society

    International Nuclear Information System (INIS)

    1996-01-01

    This is a celebration of the centenary of Rontgen''s discovery of Xrays. It is also the 50th anniversary of the first hospital physicist appointment in New Zealand. The historical element of the programme will complement the emphasis on current applications of the physical and engineering sciences to medicine and an anticipation of future developments. For the first time the Australasian College of Physical Scientists and Engineers in Medicine, together with the IEAust College of Biomedical Engineers, are joined by the Asia/Pacific Region of the IEEE Engineering in Medicine and Biology Society to make this a truly international conference. The proceedings include many papers on radiology and radiotherapy

  5. A fluorogenic molecular nanoprobe with an engineered internal environment for sensitive and selective detection of biological hydrogen sulfide.

    Science.gov (United States)

    Kim, Myung; Seo, Young Hun; Kim, Youngsun; Heo, Jeongyun; Jang, Woo-Dong; Sim, Sang Jun; Kim, Sehoon

    2017-02-14

    A nanoreactor approach based on the amphiphilic assembly of various molecules offers a chance to finely engineer the internal reaction medium to enable highly selective and sensitive detection of H 2 S in biological media, being useful for microscopic imaging of cellular processes and in vitro diagnostics with blood samples.

  6. Chitosan fibers with improved biological and mechanical properties for tissue engineering applications.

    Science.gov (United States)

    Albanna, Mohammad Z; Bou-Akl, Therese H; Blowytsky, Oksana; Walters, Henry L; Matthew, Howard W T

    2013-04-01

    The low mechanical properties of hydrogel materials such as chitosan hinder their broad utility for tissue engineering applications. Previous research efforts improved the mechanical properties of chitosan fiber through chemical and physical modifications; however, unfavorable toxicity effects on cells were reported. In this paper, we report the preparation of chitosan fibers with improved mechanical and biocompatibility properties. The structure-property relationships of extruded chitosan fibers were explored by varying acetic acid (AA) concentration, ammonia concentration, annealing temperature and degree of heparin crosslinking. Results showed that optimizing AA concentration to 2vol% improved fiber strength and stiffness by 2-fold. Extruding chitosan solution into 25wt% of ammonia solution reduced fiber diameters and improved fiber strength by 2-fold and stiffness by 3-fold, due to an increase in crystallinity as confirmed by XRD. Fiber annealing further reduced fiber diameter and improved fiber strength and stiffness as temperature increased. Chitosan fibers crosslinked with heparin had increased diameter but lower strength and stiffness properties and higher breaking strain values. When individual parameters were combined, further improvement in fiber mechanical properties was achieved. All mechanically improved fibers and heparin crosslinked fibers promoted valvular interstitial cells (VIC) attachment and growth over 10 day cultures. Our results demonstrate the ability to substantially improve the mechanical properties of chitosan fibers without adversely affecting their biological properties. The investigated treatments offer numerous advantages over previous physical/chemical modifications and thus are expected to expand the utility of chitosan fibers with tunable mechanical properties in various tissue engineering applications. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications

    International Nuclear Information System (INIS)

    Xu Tao; Binder, Kyle W; Albanna, Mohammad Z; Dice, Dennis; Zhao Weixin; Yoo, James J; Atala, Anthony

    2013-01-01

    Bioprinting is an emerging technique used to fabricate viable, 3D tissue constructs through the precise deposition of cells and hydrogels in a layer-by-layer fashion. Despite the ability to mimic the native properties of tissue, printed 3D constructs that are composed of naturally-derived biomaterials still lack structural integrity and adequate mechanical properties for use in vivo, thus limiting their development for use in load-bearing tissue engineering applications, such as cartilage. Fabrication of viable constructs using a novel multi-head deposition system provides the ability to combine synthetic polymers, which have higher mechanical strength than natural materials, with the favorable environment for cell growth provided by traditional naturally-derived hydrogels. However, the complexity and high cost associated with constructing the required robotic system hamper the widespread application of this approach. Moreover, the scaffolds fabricated by these robotic systems often lack flexibility, which further restrict their applications. To address these limitations, advanced fabrication techniques are necessary to generate complex constructs with controlled architectures and adequate mechanical properties. In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications. Electrospinning of polycaprolactone fibers was alternated with inkjet printing of rabbit elastic chondrocytes suspended in a fibrin–collagen hydrogel in order to fabricate a five-layer tissue construct of 1 mm thickness. The chondrocytes survived within the printed hybrid construct with more than 80% viability one week after printing. In addition, the cells proliferated and maintained their basic biological properties within the printed layered constructs. Furthermore, the fabricated constructs formed cartilage-like tissues both in vitro and in vivo as evidenced by the

  8. Synthesis and characterization of polyglycerols dendrimers for applications in tissue engineering biological

    International Nuclear Information System (INIS)

    Passos, E.D.; Queiroz, A.A.A. de

    2014-01-01

    Full text: Introduction: Over the last twenty years is the growing development in the manufacture of synthetic scaffold in tissue engineering applications. These new materials are based on polyglycerol dendrimers (PGLD's). PGLD's are highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Furthermore, since these materials are based on naturally occurring compounds that degrades over time in the body and can be safely excreted. The objective of this work was the synthesis, physicochemical, biological characterization of HPGL's with potential use as scaffolds in tissue engineering. HPGL's with oligomeric cores, of diglycerol triglycerol and tetraglycerol was used. Theoretical and Experimental Simulation Details: The synthesis of PGLD procedures involves the etherification of glycerol through anionic polymerization of glycidol. The PGLD's were characterized by chromatographic techniques (SEC and HPLC), spectroscopic (FTIR, 1H-NMR and 13C - NMR) electrochemical (zeta potential) and thermal analysis (DSC and TGA) techniques. The structure- activity relationships (SAR's) of compound prototype and its analogs were studied to determine the generation number (G) of the molecule responsible for the biological activity on the adhesion and cell proliferation process. A detailed study of the structure of PGLD's of G=0-4 was performed using the Hyperchem 7. 5 and Gromacs 4 software packages. The biocompatibility studies were studied by scanning electron microscopy (SEM) and fluorescence microscopy (EPF) technique after PGLD (G=0-4) blood contact. The overall electro-negativity/total charge density, dipole moment, frontier orbital's (HOMO - LUMO) and electrostatic potential maps (EPM) were calculated. The most stable form of the resulting compounds was determined by estimating the hydration energy and energy conformation. Results and Discussion: The techniques SEM and EPF

  9. Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology.

    Science.gov (United States)

    Pandey, Ramesh Prasad; Parajuli, Prakash; Koffas, Mattheos A G; Sohng, Jae Kyung

    2016-01-01

    In this review, we address recent advances made in pathway engineering, directed evolution, and systems/synthetic biology approaches employed in the production and modification of flavonoids from microbial cells. The review is divided into two major parts. In the first, various metabolic engineering and system/synthetic biology approaches used for production of flavonoids and derivatives are discussed broadly. All the manipulations/engineering accomplished on the microorganisms since 2000 are described in detail along with the biosynthetic pathway enzymes, their sources, structures of the compounds, and yield of each product. In the second part of the review, post-modifications of flavonoids by four major reactions, namely glycosylations, methylations, hydroxylations and prenylations using recombinant strains are described. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. ANALYSIS OF BASIC PSYCHOTROPIC DRUGS IN BIOLOGICAL FLUIDS AND TISSUES BY REVERSED-PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY.

    Science.gov (United States)

    Petruczynik, Anna; Waksmundzka-Hajnos, Monika

    2017-03-01

    The review of the RP HPLC analysis of basic psychotropic drugs is presented. It contains sample preparation methods with centrifugation, protein precipitation, liquid-liquid extraction (LLE), dispersive liquid-liquid microextraction (DLLME), solid-phase extraction (SPE), solid-phase microextraction (SPME), microwave-assisted extraction (MAE) and RP-HPLC analysis. Chromatographic behavior of basic drugs in aqueous media - eluents used in reversed phase systems is discussed. Methods of blocking of residue surface silanols' interaction are mentioned. Analytical methods used for the analysis are divided into parts according with the above methods: the use of low-pH eluents, the use of high-pH eluents, the use of silanol blockers, special stationary phases for basic analytes. Literature connected with the sample preparation methods and analytical systems for the drug analysis are cited in details and presented also in Table 1.

  11. Advanced 3D tools used in reverse engineering and ray tracing simulation of phased array inspection of turbine components with complex geometry

    International Nuclear Information System (INIS)

    Daks, W.; Kovacshazy, C.; Mair, D.; Ciorau, P.

    2002-01-01

    This paper outlines the practical aspects of reverse engineering and the integration of multiple pieces of software (Drafting, CNC Machining, Ray Tracing, Inspection Simulation Scenario and Phased Array UT Analysis), in order to inspect turbine components comprised of complex geometry. The CNC software, Mastercam, and design software, CADKEY/FastSURF, were used to validate the phased-array automated and manual inspection of blade root, rotor steeples and disk-blade rim attachment. The integration of a 3D part in the software engine, Imagine 3D and SimScan, as well as Tomoview analysis (specimen feature) is based on CADKEY Developer Kit - IGES/SAT file format. A generic Ray Tracing simulation for multi-probe beam was integrated into Imagine 3D. Representative examples of reference blocks and mock-ups, UT simulation and phased-array data comparison are presented. (author)

  12. Morphology of Filamentous Fungi: Linking Cellular Biology to Process Engineering Using Aspergillus niger

    Science.gov (United States)

    Krull, Rainer; Cordes, Christiana; Horn, Harald; Kampen, Ingo; Kwade, Arno; Neu, Thomas R.; Nörtemann, Bernd

    In various biotechnological processes, filamentous fungi, e.g. Aspergillus niger, are widely applied for the production of high value-added products due to their secretion efficiency. There is, however, a tangled relationship between the morphology of these microorganisms, the transport phenomena and the related productivity. The morphological characteristics vary between freely dispersed mycelia and distinct pellets of aggregated biomass. Hence, advantages and disadvantages for mycel or pellet cultivation have to be balanced out carefully. Due to this inadequate understanding of morphogenesis of filamentous microorganisms, fungal morphology, along with reproducibility of inocula of the same quality, is often a bottleneck of productivity in industrial production. To obtain an optimisation of the production process it is of great importance to gain a better understanding of the molecular and cell biology of these microorganisms as well as the approaches in biochemical engineering and particle technique, in particular to characterise the interactions between the growth conditions, cell morphology, spore-hyphae-interactions and product formation. Advances in particle and image analysis techniques as well as micromechanical devices and their applications to fungal cultivations have made available quantitative morphological data on filamentous cells. This chapter provides the ambitious aspects of this line of action, focussing on the control and characterisation of the morphology, the transport gradients and the approaches to understand the metabolism of filamentous fungi. Based on these data, bottlenecks in the morphogenesis of A. niger within the complex production pathways from gene to product should be identified and this may improve the production yield.

  13. The EBI Search engine: providing search and retrieval functionality for biological data from EMBL-EBI.

    Science.gov (United States)

    Squizzato, Silvano; Park, Young Mi; Buso, Nicola; Gur, Tamer; Cowley, Andrew; Li, Weizhong; Uludag, Mahmut; Pundir, Sangya; Cham, Jennifer A; McWilliam, Hamish; Lopez, Rodrigo

    2015-07-01

    The European Bioinformatics Institute (EMBL-EBI-https://www.ebi.ac.uk) provides free and unrestricted access to data across all major areas of biology and biomedicine. Searching and extracting knowledge across these domains requires a fast and scalable solution that addresses the requirements of domain experts as well as casual users. We present the EBI Search engine, referred to here as 'EBI Search', an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. API integration provides access to analytical tools, allowing users to further investigate the results of their search. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types including sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, together with relevant life science literature. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Engineering a collagen matrix that replicates the biological properties of native extracellular matrix.

    Science.gov (United States)

    Nam, Kwangwoo; Sakai, Yuuki; Funamoto, Seiichi; Kimura, Tsuyoshi; Kishida, Akio

    2011-01-01

    In this study, we aimed to replicate the function of native tissues that can be used in tissue engineering and regenerative medicine. The key to such replication is the preparation of an artificial collagen matrix that possesses a structure resembling that of the extracellular matrix. We, therefore, prepared a collagen matrix by fibrillogenesis in a NaCl/Na(2)HPO(4) aqueous solution using a dialysis cassette and investigated its biological behavior in vitro and in vivo. The in vitro cell adhesion and proliferation did not show any significant differences. The degradation rate in the living body could be controlled according to the preparation condition, where the collagen matrix with high water content (F-collagen matrix, >98%) showed fast degradation and collagen matrix with lower water content (T-collagen matrix, >80%) showed no degradation for 8 weeks. The degradation did not affect the inflammatory response at all and relatively faster wound healing response was observed. Comparing this result with that of collagen gel and decellularized cornea, it can be concluded that the structural factor is very important and no cell abnormal behavior would be observed for quaternary structured collagen matrix.

  15. Biological engineering applications of feedforward neural networks designed and parameterized by genetic algorithms.

    Science.gov (United States)

    Ferentinos, Konstantinos P

    2005-09-01

    Two neural network (NN) applications in the field of biological engineering are developed, designed and parameterized by an evolutionary method based on the evolutionary process of genetic algorithms. The developed systems are a fault detection NN model and a predictive modeling NN system. An indirect or 'weak specification' representation was used for the encoding of NN topologies and training parameters into genes of the genetic algorithm (GA). Some a priori knowledge of the demands in network topology for specific application cases is required by this approach, so that the infinite search space of the problem is limited to some reasonable degree. Both one-hidden-layer and two-hidden-layer network architectures were explored by the GA. Except for the network architecture, each gene of the GA also encoded the type of activation functions in both hidden and output nodes of the NN and the type of minimization algorithm that was used by the backpropagation algorithm for the training of the NN. Both models achieved satisfactory performance, while the GA system proved to be a powerful tool that can successfully replace the problematic trial-and-error approach that is usually used for these tasks.

  16. Preliminary report of biological intrusion studies at the Idaho National Engineering Laboratory subsurface disposal area

    International Nuclear Information System (INIS)

    Reynolds, T.D.; Arthur, W.J.

    1983-01-01

    As part of a larger study on the effects of biological intrusion of plants and animals into the soil cover placed over low-level radioactive wastes stored at the Idaho National Engineering Laboratory Subsurface Disposal Area (SDA), research was initiated in the summer of 1982 to determine the burrow characteristics and movement patterns of several small mammal species, and the rooting depths of various plants. The depth, length, and volume of burrows were determined for four small mammal species: deer mouse (Peromyscus maniculatus), Ord's kangaroo rat (Dipodomys ordii), montane vole (Microtus montanus), and Townsend's ground squirrel (Spermophilis townsendii). The latter species excavated the greatest mean burrow depth (39 cm), length (404 cm), and volume (14.8 1). Movement patterns of three species were determined by radiotelemetry. The mean area of use for P. maniculatus, D. ordii, and M. montanus was 2.3, 1.5, and 1.2 ha respectively. Limited data on rooting depths of various native and introduced plant species at the SDA were obtained by literature review and excavation. During FY-83, experiments will be conducted, using the information obtained from the first year of this study, to evaluate the impact of burrowing mammals and root intrusion on the integrity of the soil cover currently existing at the SDA. Details of these experimental studies are presented

  17. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    Energy Technology Data Exchange (ETDEWEB)

    Madhavan, Aravind [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Rajiv Gandhi Centre for Biotechnology, Trivandrum (India); Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran, E-mail: sindhurgcb@gmail.com; Sukumaran, Rajeev K. [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Pandey, Ashok [Biotechnology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial Research, Trivandrum (India); Center for Innovative and Applied Bioprocessing, Mohali, Punjab (India); Castro, Galliano Eulogio [Dpt. Ingeniería Química, Ambiental y de los Materiales Edificio, Universidad de Jaén, Jaén (Spain)

    2017-04-25

    The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  18. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    Directory of Open Access Journals (Sweden)

    Raveendran Sindhu

    2017-04-01

    Full Text Available The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  19. Synthetic Biology and Metabolic Engineering Approaches and Its Impact on Non-Conventional Yeast and Biofuel Production

    International Nuclear Information System (INIS)

    Madhavan, Aravind; Jose, Anju Alphonsa; Binod, Parameswaran; Sindhu, Raveendran; Sukumaran, Rajeev K.; Pandey, Ashok; Castro, Galliano Eulogio

    2017-01-01

    The increasing fossil fuel scarcity has led to an urgent need to develop alternative fuels. Currently microorganisms have been extensively used for the production of first-generation biofuels from lignocellulosic biomass. Yeast is the efficient producer of bioethanol among all existing biofuels option. Tools of synthetic biology have revolutionized the field of microbial cell factories especially in the case of ethanol and fatty acid production. Most of the synthetic biology tools have been developed for the industrial workhorse Saccharomyces cerevisiae. The non-conventional yeast systems have several beneficial traits like ethanol tolerance, thermotolerance, inhibitor tolerance, genetic diversity, etc., and synthetic biology have the power to expand these traits. Currently, synthetic biology is slowly widening to the non-conventional yeasts like Hansenula polymorpha, Kluyveromyces lactis, Pichia pastoris, and Yarrowia lipolytica. Herein, we review the basic synthetic biology tools that can apply to non-conventional yeasts. Furthermore, we discuss the recent advances employed to develop efficient biofuel-producing non-conventional yeast strains by metabolic engineering and synthetic biology with recent examples. Looking forward, future synthetic engineering tools’ development and application should focus on unexplored non-conventional yeast species.

  20. Design, Synthesis and Biological Activity of Novel Reversible Peptidyl FVIIa Inhibitors Rh-Catalyzed Enantioselective Synthesis of Diaryl Amines

    DEFF Research Database (Denmark)

    Storgaard, Morten

    functional group tolerance. Unfortunately, these -aryl tetramic acids were too unreactive and ring opening toward the synthesis of the building block did not succeed. However, -aryl tetramic acids are still interesting compounds due to their potential biological activity. The building block 3.15 (P1......-catalyzed enantioselective synthesis of diaryl amines, which is an important class of compounds (Chapter 4). For example it is found in the third generation anti-histaminic agent levocetirizine. Development of efficient synthetic routes is therefore of considerably interest. The rhodium-catalyzed enantioselective synthesis...

  1. Development of a tetrameric streptavidin mutein with reversible biotin binding capability: engineering a mobile loop as an exit door for biotin.

    Directory of Open Access Journals (Sweden)

    Valerie J O'Sullivan

    Full Text Available A novel form of tetrameric streptavidin has been engineered to have reversible biotin binding capability. In wild-type streptavidin, loop(3-4 functions as a lid for the entry and exit of biotin. When biotin is bound, interactions between biotin and key residues in loop(3-4 keep this lid in the closed state. In the engineered mutein, a second biotin exit door is created by changing the amino acid sequence of loop(7-8. This door is mobile even in the presence of the bound biotin and can facilitate the release of biotin from the mutein. Since loop(7-8 is involved in subunit interactions, alteration of this loop in the engineered mutein results in an 11° rotation between the two dimers in reference to wild-type streptavidin. The tetrameric state of the engineered mutein is stabilized by a H127C mutation, which leads to the formation of inter-subunit disulfide bonds. The biotin binding kinetic parameters (k(off of 4.28×10(-4 s(-1 and K(d of 1.9×10(-8 M make this engineered mutein a superb affinity agent for the purification of biotinylated biomolecules. Affinity matrices can be regenerated using gentle procedures, and regenerated matrices can be reused at least ten times without any observable reduction in binding capacity. With the combination of both the engineered mutein and wild-type streptavidin, biotinylated biomolecules can easily be affinity purified to high purity and immobilized to desirable platforms without any leakage concerns. Other potential biotechnological applications, such as development of an automated high-throughput protein purification system, are feasible.

  2. Development of a Tetrameric Streptavidin Mutein with Reversible Biotin Binding Capability: Engineering a Mobile Loop as an Exit Door for Biotin

    Science.gov (United States)

    O'Sullivan, Valerie J.; Barrette-Ng, Isabelle; Hommema, Eric; Hermanson, Greg T.; Schofield, Mark; Wu, Sau-Ching; Honetschlaeger, Claudia; Ng, Kenneth K.-S.; Wong, Sui-Lam

    2012-01-01

    A novel form of tetrameric streptavidin has been engineered to have reversible biotin binding capability. In wild-type streptavidin, loop3–4 functions as a lid for the entry and exit of biotin. When biotin is bound, interactions between biotin and key residues in loop3–4 keep this lid in the closed state. In the engineered mutein, a second biotin exit door is created by changing the amino acid sequence of loop7–8. This door is mobile even in the presence of the bound biotin and can facilitate the release of biotin from the mutein. Since loop7–8 is involved in subunit interactions, alteration of this loop in the engineered mutein results in an 11° rotation between the two dimers in reference to wild-type streptavidin. The tetrameric state of the engineered mutein is stabilized by a H127C mutation, which leads to the formation of inter-subunit disulfide bonds. The biotin binding kinetic parameters (koff of 4.28×10−4 s−1 and Kd of 1.9×10−8 M) make this engineered mutein a superb affinity agent for the purification of biotinylated biomolecules. Affinity matrices can be regenerated using gentle procedures, and regenerated matrices can be reused at least ten times without any observable reduction in binding capacity. With the combination of both the engineered mutein and wild-type streptavidin, biotinylated biomolecules can easily be affinity purified to high purity and immobilized to desirable platforms without any leakage concerns. Other potential biotechnological applications, such as development of an automated high-throughput protein purification system, are feasible. PMID:22536357

  3. GRASP/Ada (Graphical Representations of Algorithms, Structures, and Processes for Ada): The development of a program analysis environment for Ada. Reverse engineering tools for Ada, task 1, phase 2

    Science.gov (United States)

    Cross, James H., II

    1990-01-01

    The study, formulation, and generation of structures for Ada (GRASP/Ada) are discussed in this second phase report of a three phase effort. Various graphical representations that can be extracted or generated from source code are described and categorized with focus on reverse engineering. The overall goal is to provide the foundation for a CASE (computer-aided software design) environment in which reverse engineering and forward engineering (development) are tightly coupled. Emphasis is on a subset of architectural diagrams that can be generated automatically from source code with the control structure diagram (CSD) included for completeness.

  4. A Standard Addition Method to Assay the Concentration of Biologically Interesting Polyphenols in Grape Berries by Reversed-Phase HPLC

    Directory of Open Access Journals (Sweden)

    Serkos A. Haroutounian

    2007-09-01

    Full Text Available A reversed-phase HPLC method which allows the simultaneous assay of (+- catechin, (–-epicatechin, trans-resveratrol, quercetin and quercetin glycosides in grape berries is described. Kromasil 100 served as stationary phase and a gradient of acetic acid, water and methanol was used. The analytical run requires 42 min for complete sample elution. Satisfactory peak resolution was achieved following a novel extraction process and direct injection of a 20 μL sample. The method was used for the analyses of eighteen samples. Linearities were in the range of 0.98 to 0.999 regression coefficient, for all phenolics, while detection limits ranged from 30 μg mL–1 for trans-resveratrol to 1.5 mg mL–1 for (+-catechin. Recoveries ranged from 95.1 to 98.7% while the method provided good precision, with standard deviations between 3.5 and 6.1%, n=5.

  5. Evolutionary approaches for the reverse-engineering of gene regulatory networks: A study on a biologically realistic dataset

    Directory of Open Access Journals (Sweden)

    Gidrol Xavier

    2008-02-01

    Full Text Available Abstract Background Inferring gene regulatory networks from data requires the development of algorithms devoted to structure extraction. When only static data are available, gene interactions may be modelled by a Bayesian Network (BN that represents the presence of direct interactions from regulators to regulees by conditional probability distributions. We used enhanced evolutionary algorithms to stochastically evolve a set of candidate BN structures and found the model that best fits data without prior knowledge. Results We proposed various evolutionary strategies suitable for the task and tested our choices using simulated data drawn from a given bio-realistic network of 35 nodes, the so-called insulin network, which has been used in the literature for benchmarking. We assessed the inferred models against this reference to obtain statistical performance results. We then compared performances of evolutionary algorithms using two kinds of recombination operators that operate at different scales in the graphs. We introduced a niching strategy that reinforces diversity through the population and avoided trapping of the algorithm in one local minimum in the early steps of learning. We show the limited effect of the mutation operator when niching is applied. Finally, we compared our best evolutionary approach with various well known learning algorithms (MCMC, K2, greedy search, TPDA, MMHC devoted to BN structure learning. Conclusion We studied the behaviour of an evolutionary approach enhanced by niching for the learning of gene regulatory networks with BN. We show that this approach outperforms classical structure learning methods in elucidating the original model. These results were obtained for the learning of a bio-realistic network and, more importantly, on various small datasets. This is a suitable approach for learning transcriptional regulatory networks from real datasets without prior knowledge.

  6. Synthesis and characterization of polyglycerols dendrimers for applications in tissue engineering biological

    Energy Technology Data Exchange (ETDEWEB)

    Passos, E.D.; Queiroz, A.A.A. de [Universidade Federal de Itajuba (UNIFEI), MG (Brazil)

    2014-07-01

    Full text: Introduction: Over the last twenty years is the growing development in the manufacture of synthetic scaffold in tissue engineering applications. These new materials are based on polyglycerol dendrimers (PGLD's). PGLD's are highly functional polymers with hydroxymethyl side groups, fulfill all structural prerequisites to replace poly(ethylene glycol)s in medical applications. Furthermore, since these materials are based on naturally occurring compounds that degrades over time in the body and can be safely excreted. The objective of this work was the synthesis, physicochemical, biological characterization of HPGL's with potential use as scaffolds in tissue engineering. HPGL's with oligomeric cores, of diglycerol triglycerol and tetraglycerol was used. Theoretical and Experimental Simulation Details: The synthesis of PGLD procedures involves the etherification of glycerol through anionic polymerization of glycidol. The PGLD's were characterized by chromatographic techniques (SEC and HPLC), spectroscopic (FTIR, 1H-NMR and 13C - NMR) electrochemical (zeta potential) and thermal analysis (DSC and TGA) techniques. The structure- activity relationships (SAR's) of compound prototype and its analogs were studied to determine the generation number (G) of the molecule responsible for the biological activity on the adhesion and cell proliferation process. A detailed study of the structure of PGLD's of G=0-4 was performed using the Hyperchem 7. 5 and Gromacs 4 software packages. The biocompatibility studies were studied by scanning electron microscopy (SEM) and fluorescence microscopy (EPF) technique after PGLD (G=0-4) blood contact. The overall electro-negativity/total charge density, dipole moment, frontier orbital's (HOMO - LUMO) and electrostatic potential maps (EPM) were calculated. The most stable form of the resulting compounds was determined by estimating the hydration energy and energy conformation. Results and

  7. Promoting convergence: The integrated graduate program in physical and engineering biology at Yale University, a new model for graduate education.

    Science.gov (United States)

    Noble, Dorottya B; Mochrie, Simon G J; O'Hern, Corey S; Pollard, Thomas D; Regan, Lynne

    2016-11-12

    In 2008, we established the Integrated Graduate Program in Physical and Engineering Biology (IGPPEB) at Yale University. Our goal was to create a comprehensive graduate program to train a new generation of scientists who possess a sophisticated understanding of biology and who are capable of applying physical and quantitative methodologies to solve biological problems. Here we describe the framework of the training program, report on its effectiveness, and also share the insights we gained during its development and implementation. The program features co-teaching by faculty with complementary specializations, student peer learning, and novel hands-on courses that facilitate the seamless blending of interdisciplinary research and teaching. It also incorporates enrichment activities to improve communication skills, engage students in science outreach, and foster a cohesive program cohort, all of which promote the development of transferable skills applicable in a variety of careers. The curriculum of the graduate program is integrated with the curricular requirements of several Ph.D.-granting home programs in the physical, engineering, and biological sciences. Moreover, the wide-ranging recruiting activities of the IGPPEB serve to enhance the quality and diversity of students entering graduate school at Yale. We also discuss some of the challenges we encountered in establishing and optimizing the program, and describe the institution-level changes that were catalyzed by the introduction of the new graduate program. The goal of this article is to serve as both an inspiration and as a practical "how to" manual for those who seek to establish similar programs at their own institutions. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(6):537-549, 2016. © 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology.

  8. Using Mathematics and Engineering to Solve Problems in Secondary Level Biology

    Science.gov (United States)

    Cox, Charles; Reynolds, Birdy; Schunn, Christian; Schuchardt, Anita

    2016-01-01

    There are strong classroom ties between mathematics and the sciences of physics and chemistry, but those ties seem weaker between mathematics and biology. Practicing biologists realize both that there are interesting mathematics problems in biology, and that viewing classroom biology in the context of another discipline could support students'…

  9. Molecular Cloning Designer Simulator (MCDS: All-in-one molecular cloning and genetic engineering design, simulation and management software for complex synthetic biology and metabolic engineering projects

    Directory of Open Access Journals (Sweden)

    Zhenyu Shi

    2016-12-01

    Full Text Available Molecular Cloning Designer Simulator (MCDS is a powerful new all-in-one cloning and genetic engineering design, simulation and management software platform developed for complex synthetic biology and metabolic engineering projects. In addition to standard functions, it has a number of features that are either unique, or are not found in combination in any one software package: (1 it has a novel interactive flow-chart user interface for complex multi-step processes, allowing an integrated overview of the whole project; (2 it can perform a user-defined workflow of cloning steps in a single execution of the software; (3 it can handle multiple types of genetic recombineering, a technique that is rapidly replacing classical cloning for many applications; (4 it includes experimental information to conveniently guide wet lab work; and (5 it can store results and comments to allow the tracking and management of the whole project in one platform. MCDS is freely available from https://mcds.codeplex.com. Keywords: BioCAD, Genetic engineering software, Molecular cloning software, Synthetic biology, Workflow simulation and management

  10. Use of micro computed-tomography and 3D printing for reverse engineering of mouse embryo nasal capsule

    International Nuclear Information System (INIS)

    Tesařová, M.; Zikmund, T.; Kaiser, J.; Kaucká, M.; Adameyko, I.; Jaroš, J.; Paloušek, D.; Škaroupka, D.

    2016-01-01

    Imaging of increasingly complex cartilage in vertebrate embryos is one of the key tasks of developmental biology. This is especially important to study shape-organizing processes during initial skeletal formation and growth. Advanced imaging techniques that are reflecting biological needs give a powerful impulse to push the boundaries of biological visualization. Recently, techniques for contrasting tissues and organs have improved considerably, extending traditional 2D imaging approaches to 3D . X-ray micro computed tomography (μCT), which allows 3D imaging of biological objects including their internal structures with a resolution in the micrometer range, in combination with contrasting techniques seems to be the most suitable approach for non-destructive imaging of embryonic developing cartilage. Despite there are many software-based ways for visualization of 3D data sets, having a real solid model of the studied object might give novel opportunities to fully understand the shape-organizing processes in the developing body. In this feasibility study we demonstrated the full procedure of creating a real 3D object of mouse embryo nasal capsule, i.e. the staining, the μCT scanning combined by the advanced data processing and the 3D printing

  11. Applications of Engineered DNA-Binding Molecules Such as TAL Proteins and the CRISPR/Cas System in Biology Research

    Directory of Open Access Journals (Sweden)

    Toshitsugu Fujita

    2015-09-01

    Full Text Available Engineered DNA-binding molecules such as transcription activator-like effector (TAL or TALE proteins and the clustered regularly interspaced short palindromic repeats (CRISPR and CRISPR-associated proteins (Cas (CRISPR/Cas system have been used extensively for genome editing in cells of various types and species. The sequence-specific DNA-binding activities of these engineered DNA-binding molecules can also be utilized for other purposes, such as transcriptional activation, transcriptional repression, chromatin modification, visualization of genomic regions, and isolation of chromatin in a locus-specific manner. In this review, we describe applications of these engineered DNA-binding molecules for biological purposes other than genome editing.

  12. A proposal to enhance Engineering education in biology and Medicine by following the legacy of René Favaloro.

    Science.gov (United States)

    Armentano, Ricardo L; Cardelino, Juan; Wray, Sandra; Cymberknop, Leandro J; Kun, Luis

    2015-01-01

    The synergy amongst Engineering, Medicine and Biology evolves as fast as these disciplines. We propose to articulate these specialties based on the premise that new professionals must face different situations or crisis due to the so-called islands of excellence. René Favaloro focused his work and struggles against poverty, since malnutrition and environmental degradation may increase the propensity to cardiovascular diseases. Doctor Favaloro has dedicated, throughout his career, a considerable amount of time to prepare and qualify a research group, aware of the importance that an adequate working environment has over the final results. He created a team of young students, engineers, medical doctors, physicists, mathematicians and other specialists. He centered his attention on human resources, in order to disseminate his latest advances in Biology, Medicine and Engineering. We are revising the programs of biomedical engineering education and the application of new pedagogic paradigms, where critical thinking is the key: a holistic challenge that consists of a new way of learning, innovating, communicating and shearing, with a creative attitude that represents quality of perception.

  13. An Interdisciplinary Approach for Biology, Technology, Engineering and Mathematics (BTEM to Enhance 21st Century Skills in Malaysia.

    Directory of Open Access Journals (Sweden)

    Lee Chuo Hiong

    2015-07-01

    Full Text Available An interdisciplinary approach for Biology, Technology, Engineering and Mathematics (BTEM is suggested to develop 21st century skills in the Malaysian context. BTEM allows students to master biological knowledge and at the same time to be adroit in other sub discipline skills. Students master factual knowledge of biology and skills of the 21st century simultaneously. The two main teaching and learning strategies applied in BTEM are problem-based learning and inquiry-based learning. Students are exposed to real world problems that require them to undergo inquiry processes to discover the inventive solutions. The content knowledge of biology adheres to the Malaysian Integrated Curriculum for Secondary Schools. The essence of engineering is inventive problem solving. Incorporation of information communication technologies in teaching and learning will be able to fulfil the needs of the current Net Generation. Mathematics plays an important role as computational tools, especially in analysing data. The highlighted 21st century skills in BTEM include digital literacy, inventive thinking, effective communication, high productivity, and spiritual and noble values.

  14. ARACNe-AP: Gene Network Reverse Engineering through Adaptive Partitioning inference of Mutual Information. | Office of Cancer Genomics

    Science.gov (United States)

    The accurate reconstruction of gene regulatory networks from large scale molecular profile datasets represents one of the grand challenges of Systems Biology. The Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) represents one of the most effective tools to accomplish this goal. However, the initial Fixed Bandwidth (FB) implementation is both inefficient and unable to deal with sample sets providing largely uneven coverage of the probability density space.

  15. Cigarette company trade secrets are not secret: an analysis of reverse engineering reports in internal tobacco industry documents released as a result of litigation.

    Science.gov (United States)

    Velicer, Clayton; Lempert, Lauren K; Glantz, Stanton

    2015-09-01

    Use previously secret tobacco industry documents to assess tobacco companies' routine claims of trade secret protection for information on cigarette ingredients, additives and construction made to regulatory agencies, as well as the companies' refusal to publicly disclose this information. We analysed previously secret tobacco industry documents available at (http://legacy.library.ucsf.edu) to identify 100 examples of seven major tobacco companies' reverse engineering of their competitors' brands between 1937 and 2001. These reverse engineering reports contain detailed data for 142 different measurements for at least two companies, including physical parameters of the cigarettes, tobacco types, humectants, additives, flavourings, and smoke constituents of competitors' cigarettes. These 100 documents were distributed to 564 employees, including top managers in domestic and foreign offices across multiple departments, including executive leadership, research and design, product development, marketing and legal. These documents reported new competitors' products, measured ingredient changes over time, and informed companies' decisions regarding ingredients in their own products. Because cigarette companies routinely analyse their competitors' cigarettes in great detail, this information is neither secret nor commercially valuable and, thus, does not meet the legal definition of a 'trade secret.' This information is only being kept 'secret' from the people consuming cigarettes and the scientific community. Public agencies should release this detailed information because it would provide valuable information about how ingredients affect addictiveness and toxicity, and would help the public health community and consumers better understand the impact of cigarette design on human health. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Synthetic biology approaches in cancer immunotherapy, genetic network engineering, and genome editing.

    Science.gov (United States)

    Chakravarti, Deboki; Cho, Jang Hwan; Weinberg, Benjamin H; Wong, Nicole M; Wong, Wilson W

    2016-04-18

    Investigations into cells and their contents have provided evolving insight into the emergence of complex biological behaviors. Capitalizing on this knowledge, synthetic biology seeks to manipulate the cellular machinery towards novel purposes, extending discoveries from basic science to new applications. While these developments have demonstrated the potential of building with biological parts, the complexity of cells can pose numerous challenges. In this review, we will highlight the broad and vital role that the synthetic biology approach has played in applying fundamental biological discoveries in receptors, genetic circuits, and genome-editing systems towards translation in the fields of immunotherapy, biosensors, disease models and gene therapy. These examples are evidence of the strength of synthetic approaches, while also illustrating considerations that must be addressed when developing systems around living cells.

  17. X-ray diffraction and infrared spectroscopy analyses on the crystallinity of engineered biological hydroxyapatite for medical application

    Science.gov (United States)

    Poralan, G. M., Jr.; Gambe, J. E.; Alcantara, E. M.; Vequizo, R. M.

    2015-06-01

    Biological hydroxyapatite (BHAp) derived from thermally-treated fish bones was successfully produced. However, the obtained biological HAp was amorphous and thus making it unfavorable for medical application. Consequently, this research exploits and engineers the crystallinity of BHAp powders by addition of CaCO3 and investigates its degree of crystallinity using XRD and IR spectroscopy. On XRD, the HAp powders with [Ca]/[P] ratios 1.42, 1.46, 1.61 and 1.93 have degree of crystallinity equal to 58.08, 72.13, 85.79, 75.85% and crystal size equal to 0.67, 0.74, 0.75, 0.72 nm, respectively. The degree of crystallinity and crystal size of the obtained calcium deficient biological HAp powders increase as their [Ca]/[P] ratio approaches the stoichiometric ratio by addition of CaCO3 as source of Ca2+ ions. These results show the possibility of engineering the crystallinity and crystal size of biological HAp by addition of CaCO3. Moreover, the splitting factor of PO4 vibration matches the result with % crystallinity on XRD. Also, the area of phosphate-substitution site of PO4 vibration shows linear relationship (R2 = 0.994) with crystal size calculated from XRD. It is worth noting that the crystallinity of the biological HAp with [Ca]/[P] ratios 1.42 and 1.48 fall near the range 60-70% for highly resorbable HAp used in the medical application.

  18. BioTCM-SE: a semantic search engine for the information retrieval of modern biology and traditional Chinese medicine.

    Science.gov (United States)

    Chen, Xi; Chen, Huajun; Bi, Xuan; Gu, Peiqin; Chen, Jiaoyan; Wu, Zhaohui

    2014-01-01

    Understanding the functional mechanisms of the complex biological system as a whole is drawing more and more attention in global health care management. Traditional Chinese Medicine (TCM), essentially different from Western Medicine (WM), is gaining increasing attention due to its emphasis on individual wellness and natural herbal medicine, which satisfies the goal of integrative medicine. However, with the explosive growth of biomedical data on the Web, biomedical researchers are now confronted with the problem of large-scale data analysis and data query. Besides that, biomedical data also has a wide coverage which usually comes from multiple heterogeneous data sources and has different taxonomies, making it hard to integrate and query the big biomedical data. Embedded with domain knowledge from different disciplines all regarding human biological systems, the heterogeneous data repositories are implicitly connected by human expert knowledge. Traditional search engines cannot provide accurate and comprehensive search results for the semantically associated knowledge since they only support keywords-based searches. In this paper, we present BioTCM-SE, a semantic search engine for the information retrieval of modern biology and TCM, which provides biologists with a comprehensive and accurate associated knowledge query platform to greatly facilitate the implicit knowledge discovery between WM and TCM.

  19. BioTCM-SE: A Semantic Search Engine for the Information Retrieval of Modern Biology and Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Xi Chen

    2014-01-01

    Full Text Available Understanding the functional mechanisms of the complex biological system as a whole is drawing more and more attention in global health care management. Traditional Chinese Medicine (TCM, essentially different from Western Medicine (WM, is gaining increasing attention due to its emphasis on individual wellness and natural herbal medicine, which satisfies the goal of integrative medicine. However, with the explosive growth of biomedical data on the Web, biomedical researchers are now confronted with the problem of large-scale data analysis and data query. Besides that, biomedical data also has a wide coverage which usually comes from multiple heterogeneous data sources and has different taxonomies, making it hard to integrate and query the big biomedical data. Embedded with domain knowledge from different disciplines all regarding human biological systems, the heterogeneous data repositories are implicitly connected by human expert knowledge. Traditional search engines cannot provide accurate and comprehensive search results for the semantically associated knowledge since they only support keywords-based searches. In this paper, we present BioTCM-SE, a semantic search engine for the information retrieval of modern biology and TCM, which provides biologists with a comprehensive and accurate associated knowledge query platform to greatly facilitate the implicit knowledge discovery between WM and TCM.

  20. Using Synthetic Biology to Engineer Living Cells That Interface with Programmable Materials.

    Science.gov (United States)

    Heyde, Keith C; Scott, Felicia Y; Paek, Sung-Ho; Zhang, Ruihua; Ruder, Warren C

    2017-03-09

    We have developed an abiotic-biotic interface that allows engineered cells to control the material properties of a functionalized surface. This system is made by creating two modules: a synthetically engineered strain of E. coli cells and a functionalized material interface. Within this paper, we detail a protocol for genetically engineering selected behaviors within a strain of E. coli using molecular cloning strategies. Once developed, this strain produces elevated levels of biotin when exposed to a chemical inducer. Additionally, we detail protocols for creating two different functionalized surfaces, each of which is able to respond to cell-synthesized biotin. Taken together, we present a methodology for creating a linked, abiotic-biotic system that allows engineered cells to control material composition and assembly on nonliving substrates.

  1. Computation: A New Open Access Journal of Computational Chemistry, Computational Biology and Computational Engineering

    OpenAIRE

    Karlheinz Schwarz; Rainer Breitling; Christian Allen

    2013-01-01

    Computation (ISSN 2079-3197; http://www.mdpi.com/journal/computation) is an international scientific open access journal focusing on fundamental work in the field of computational science and engineering. Computational science has become essential in many research areas by contributing to solving complex problems in fundamental science all the way to engineering. The very broad range of application domains suggests structuring this journal into three sections, which are briefly characterized ...

  2. Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H.

    Science.gov (United States)

    Kankanala, Jayakanth; Kirby, Karen A; Huber, Andrew D; Casey, Mary C; Wilson, Daniel J; Sarafianos, Stefan G; Wang, Zhengqiang

    2017-12-01

    Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have shown significant antiviral activities. We report herein the design, synthesis and biological evaluation of a novel N-hydroxy thienopyrimidine-2,3-dione chemotype (11) which potently and selectively inhibited RNase H with considerable potency against HIV-1 in cell culture. Current structure-activity-relationship (SAR) identified analogue 11d as a nanomolar inhibitor of RNase H (IC 50  = 0.04 μM) with decent antiviral potency (EC 50  = 7.4 μM) and no cytotoxicity (CC 50  > 100 μM). In extended biochemical assays compound 11d did not inhibit RT polymerase (pol) while inhibiting integrase strand transfer (INST) with 53 fold lower potency (IC 50  = 2.1 μM) than RNase H inhibition. Crystallographic and molecular modeling studies confirmed the RNase H active site binding mode. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Geomagnetic Reversals during the Phanerozoic.

    Science.gov (United States)

    McElhinny, M W

    1971-04-09

    An antalysis of worldwide paleomagnetic measurements suggests a periodicity of 350 x 10(6) years in the polarity of the geomagnetic field. During the Mesozoic it is predominantly normal, whereas during the Upper Paleozoic it is predominantly reversed. Although geomagnetic reversals occur at different rates throughout the Phanerozoic, there appeaars to be no clear correlation between biological evolutionary rates and reversal frequency.

  4. Can Man Control His Biological Evolution? A Symposium on Genetic Engineering. Man's Responsibility to His Future

    Science.gov (United States)

    Hoagland, Hudson

    1972-01-01

    Biological evolution can be carried out in the laboratory. With new knowledge available in genetics, possibilities are raised that genetic characters can be transferred in the future to embryos according to a predetermined plan. (PS)

  5. Proceedings of the ninth annual conference of the IEEE Engineering in Medicine and Biology Society

    International Nuclear Information System (INIS)

    Anon.

    1987-01-01

    This book contains over 100 papers. Some of the titles are: Angular integrations and inter-projections correlation effects in CT reconstruction; Supercomputing environment for biomedical research; Program towards a computational molecular biology; Current problems in molecular biology computing; Signal averaging applied to positron emission tomography; First experimental results from a high spatial resolution PET prototype; and A coherent approach in computer-aided radiotherapy

  6. Reverse Algols

    Science.gov (United States)

    Leung, K. C.

    1989-01-01

    Reverse Algols, binary systems with a semidetached configuration in which the more massive component is in contact with the critical equipotential surface, are examined. Observational evidence for reverse Algols is presented and the parameters of seven reverse Algols are listed. The evolution of Algols and reverse Algols is discussed. It is suggested that, because reverse Algols represent the premass-reversal semidetached phase of close binary evolution, the evolutionary time scale between regular and reverse Algols is the ratio of the number of confirmed systems of these two Algol types.

  7. Suitability of a PLCL fibrous scaffold for soft tissue engineering applications: A combined biological and mechanical characterisation.

    Science.gov (United States)

    Laurent, Cédric P; Vaquette, Cédryck; Liu, Xing; Schmitt, Jean-François; Rahouadj, Rachid

    2018-04-01

    Poly(lactide-co-ε-caprolactone) (PLCL) has been reported to be a good candidate for tissue engineering because of its good biocompatibility. Particularly, a braided PLCL scaffold (PLL/PCL ratio = 85/15) has been recently designed and partially validated for ligament tissue engineering. In the present study, we assessed the in vivo biocompatibility of acellular and cellularised scaffolds in a rat model. We then determined its in vitro biocompatibility using stem cells issued from both bone marrow and Wharton Jelly. From a biological point of view, the scaffold was shown to be suitable for tissue engineering in all these cases. Secondly, while the initial mechanical properties of this scaffold have been previously reported to be adapted to load-bearing applications, we studied the evolution in time of the mechanical properties of PLCL fibres due to hydrolytic degradation. Results for isolated PLCL fibres were extrapolated to the fibrous scaffold using a previously developed numerical model. It was shown that no accumulation of plastic strain was to be expected for a load-bearing application such as anterior cruciate ligament tissue engineering. However, PLCL fibres exhibited a non-expected brittle behaviour after two months. This may involve a potential risk of premature failure of the scaffold, unless tissue growth compensates this change in mechanical properties. This combined study emphasises the need to characterise the properties of biomaterials in a pluridisciplinary approach, since biological and mechanical characterisations led in this case to different conclusions concerning the suitability of this scaffold for load-bearing applications.

  8. Reverse engineering of logic-based differential equation models using a mixed-integer dynamic optimization approach.

    Science.gov (United States)

    Henriques, David; Rocha, Miguel; Saez-Rodriguez, Julio; Banga, Julio R

    2015-09-15

    Systems biology models can be used to test new hypotheses formulated on the basis of previous knowledge or new experimental data, contradictory with a previously existing model. New hypotheses often come in the shape of a set of possible regulatory mechanisms. This search is usually not limited to finding a single regulation link, but rather a combination of links subject to great uncertainty or no information about the kinetic parameters. In this work, we combine a logic-based formalism, to describe all the possible regulatory structures for a given dynamic model of a pathway, with mixed-integer dynamic optimization (MIDO). This framework aims to simultaneously identify the regulatory structure (represented by binary parameters) and the real-valued parameters that are consistent with the available experimental data, resulting in a logic-based differential equation model. The alternative to this would be to perform real-valued parameter estimation for each possible model structure, which is not tractable for models of the size presented in this work. The performance of the method presented here is illustrated with several case studies: a synthetic pathway problem of signaling regulation, a two-component signal transduction pathway in bacterial homeostasis, and a signaling network in liver cancer cells. Supplementary data are available at Bioinformatics online. julio@iim.csic.es or saezrodriguez@ebi.ac.uk. © The Author 2015. Published by Oxford University Press.

  9. Three-dimensional topography of the gingival line of young adult maxillary teeth: curve averaging using reverse-engineering methods.

    Science.gov (United States)

    Park, Young-Seok; Chang, Mi-Sook; Lee, Seung-Pyo

    2011-01-01

    This study attempted to establish three-dimensional average curves of the gingival line of maxillary teeth using reconstructed virtual models to utilize as guides for dental implant restorations. Virtual models from 100 full-mouth dental stone cast sets were prepared with a three-dimensional scanner and special reconstruction software. Marginal gingival lines were defined by transforming the boundary points to the NURBS (nonuniform rational B-spline) curve. Using an iterative closest point algorithm, the sample models were aligned and the gingival curves were isolated. Each curve was tessellated by 200 points using a uniform interval. The 200 tessellated points of each sample model were averaged according to the index of each model. In a pilot experiment, regression and fitting analysis of one obtained average curve was performed to depict it as mathematical formulae. The three-dimensional average curves of six maxillary anterior teeth, two maxillary right premolars, and a maxillary right first molar were obtained, and their dimensions were measured. Average curves of the gingival lines of young people were investigated. It is proposed that dentists apply these data to implant platforms or abutment designs to achieve ideal esthetics. The curves obtained in the present study may be incorporated as a basis for implant component design to improve the biologic nature and related esthetics of restorations.

  10. The logic of the floral transition: Reverse-engineering the switch controlling the identity of lateral organs.

    Directory of Open Access Journals (Sweden)

    Jean-Louis Dinh

    2017-09-01

    Full Text Available Much laboratory work has been carried out to determine the gene regulatory network (GRN that results in plant cells becoming flowers instead of leaves. However, this also involves the spatial distribution of different cell types, and poses the question of whether alternative networks could produce the same set of observed results. This issue has been addressed here through a survey of the published intercellular distribution of expressed regulatory genes and techniques both developed and applied to Boolean network models. This has uncovered a large number of models which are compatible with the currently available data. An exhaustive exploration had some success but proved to be unfeasible due to the massive number of alternative models, so genetic programming algorithms have also been employed. This approach allows exploration on the basis of both data-fitting criteria and parsimony of the regulatory processes, ruling out biologically unrealistic mechanisms. One of the conclusions is that, despite the multiplicity of acceptable models, an overall structure dominates, with differences mostly in alternative fine-grained regulatory interactions. The overall structure confirms the known interactions, including some that were not present in the training set, showing that current data are sufficient to determine the overall structure of the GRN. The model stresses the importance of relative spatial location, through explicit references to this aspect. This approach also provides a quantitative indication of how likely some regulatory interactions might be, and can be applied to the study of other developmental transitions.

  11. The logic of the floral transition: Reverse-engineering the switch controlling the identity of lateral organs.

    Science.gov (United States)

    Dinh, Jean-Louis; Farcot, Etienne; Hodgman, Charlie

    2017-09-01

    Much laboratory work has been carried out to determine the gene regulatory network (GRN) that results in plant cells becoming flowers instead of leaves. However, this also involves the spatial distribution of different cell types, and poses the question of whether alternative networks could produce the same set of observed results. This issue has been addressed here through a survey of the published intercellular distribution of expressed regulatory genes and techniques both developed and applied to Boolean network models. This has uncovered a large number of models which are compatible with the currently available data. An exhaustive exploration had some success but proved to be unfeasible due to the massive number of alternative models, so genetic programming algorithms have also been employed. This approach allows exploration on the basis of both data-fitting criteria and parsimony of the regulatory processes, ruling out biologically unrealistic mechanisms. One of the conclusions is that, despite the multiplicity of acceptable models, an overall structure dominates, with differences mostly in alternative fine-grained regulatory interactions. The overall structure confirms the known interactions, including some that were not present in the training set, showing that current data are sufficient to determine the overall structure of the GRN. The model stresses the importance of relative spatial location, through explicit references to this aspect. This approach also provides a quantitative indication of how likely some regulatory interactions might be, and can be applied to the study of other developmental transitions.

  12. Reverse Logistics

    OpenAIRE

    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  13. Chemical and biological sensors based on defect-engineered graphene mesh field-effect transistors.

    Science.gov (United States)

    Cho, Seunghee H; Kwon, Sun Sang; Yi, Jaeseok; Park, Won Il

    2016-01-01

    Graphene has been intensively studied for applications to high-performance sensors, but the sensing characteristics of graphene devices have varied from case to case, and the sensing mechanism has not been satisfactorily determined thus far. In this review, we describe recent progress in engineering of the defects in graphene grown by a silica-assisted chemical vapor deposition technique and elucidate the effect of the defects upon the electrical response of graphene sensors. This review provides guidelines for engineering and/or passivating defects to improve sensor performance and reliability.

  14. Systems biology and metabolic engineering of lactic acid bacteria for improved fermented foods

    NARCIS (Netherlands)

    Flahaut, N.A.L.; Vos, de W.M.

    2014-01-01

    Lactic acid bacteria have long been used in industrial dairy and other food fermentations that make use of their metabolic activities leading to products with specific organoleptic properties. Metabolic engineering is a rational approach to steer fermentations toward the production of desired

  15. A Transient 3D-CFD Model Incorporating Biological Processes for Use in Tissue Engineering

    DEFF Research Database (Denmark)

    Krühne, Ulrich; Wendt, D.; Martin, I.

    2010-01-01

    after 2, 8 and 13 days. The development of the cells is compared to the simulated growth of cells and it is attempted to draw a conclusion about the impact of the shear stress on the cell growth. Keyword: Computational fluid dynamics (CFD),Micro pores,Scaffold,Bioreactor,Fluid structure interaction,Tissue...... engineering...

  16. Enhancing the Internationalisation of Distance Education in the Biological Sciences: The DUNE Project and Genetic Engineering.

    Science.gov (United States)

    Leach, C. K.; And Others

    1997-01-01

    Describes the Distance Educational Network of Europe (DUNE) project that aims at enhancing the development of distance education in an international context. Highlights issues relating to the delivery of distance-learning courses in a transnational forum. Describes the genetic engineering course that aims at explaining the core techniques of…

  17. QM/MM hybrid calculation of biological macromolecules using a new interface program connecting QM and MM engines

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, Yohsuke; Tateno, Masaru [Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba Science City, Ibaraki 305-8571 (Japan); Ohta, Takehiro [Center for Computational Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba Science City, Ibaraki 305-8577 (Japan)], E-mail: tateno@ccs.tsukuba.ac.jp

    2009-02-11

    An interface program connecting a quantum mechanics (QM) calculation engine, GAMESS, and a molecular mechanics (MM) calculation engine, AMBER, has been developed for QM/MM hybrid calculations. A protein-DNA complex is used as a test system to investigate the following two types of QM/MM schemes. In a 'subtractive' scheme, electrostatic interactions between QM/MM regions are truncated in QM calculations; in an 'additive' scheme, long-range electrostatic interactions within a cut-off distance from QM regions are introduced into one-electron integration terms of a QM Hamiltonian. In these calculations, 338 atoms are assigned as QM atoms using Hartree-Fock (HF)/density functional theory (DFT) hybrid all-electron calculations. By comparing the results of the additive and subtractive schemes, it is found that electronic structures are perturbed significantly by the introduction of MM partial charges surrounding QM regions, suggesting that biological processes occurring in functional sites are modulated by the surrounding structures. This also indicates that the effects of long-range electrostatic interactions involved in the QM Hamiltonian are crucial for accurate descriptions of electronic structures of biological macromolecules.

  18. A systems biology approach to the pathogenesis of obesity-related nonalcoholic fatty liver disease using reverse phase protein microarrays for multiplexed cell signaling analysis.

    Science.gov (United States)

    Calvert, Valerie S; Collantes, Rochelle; Elariny, Hazem; Afendy, Arian; Baranova, Ancha; Mendoza, Michael; Goodman, Zachary; Liotta, Lance A; Petricoin, Emanuel F; Younossi, Zobair M

    2007-07-01

    Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Omental adipose tissue, a biologically active organ secreting adipokines and cytokines, may play a role in the development of NAFLD. We tested this hypothesis with reverse-phase protein microarrays (RPA) for multiplexed cell signaling analysis of adipose tissue from patients with NAFLD. Omental adipose tissue was obtained from 99 obese patients. Liver biopsies obtained at the time of surgery were all read by the same hepatopathologist. Adipose tissue was exposed to rapid pressure cycles to extract protein lysates. RPA was used to investigate intracellular signaling. Analysis of 54 different kinase substrates and cell signaling endpoints showed that an insulin signaling pathway is deranged in different locations in NAFLD patients. Furthermore, components of insulin receptor-mediated signaling differentiate most of the conditions on the NAFLD spectrum. For example, PKA (protein kinase A) and AKT/mTOR (protein kinase B/mammalian target of rapamycin) pathway derangement accurately discriminates patients with NASH from those with the non-progressive forms of NAFLD. PKC (protein kinase C) delta, AKT, and SHC phosphorylation changes occur in patients with simple steatosis. Amounts of the FKHR (forkhead factor Foxo1)phosphorylated at S256 residue were significantly correlated with AST/ALT ratio in all morbidly obese patients. Furthermore, amounts of cleaved caspase 9 and pp90RSK S380 were positively correlated in patients with NASH. Specific insulin pathway signaling events are altered in the adipose tissue of patients with NASH compared with patients with nonprogressive forms of NAFLD. These findings provide evidence for the role of omental fat in the pathogenesis, and potentially, the progression of NAFLD.

  19. Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering

    NARCIS (Netherlands)

    Menolascina, F.; Bellomo, D.; Maiwald, T.; Bevilacqua, V.; Ciminelli, C.; Paradiso, A.; Tommasi, S.

    2009-01-01

    Background: Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the

  20. Recent developments in systems biology and metabolic engineering of plant microbe interactions

    Directory of Open Access Journals (Sweden)

    Vishal Kumar

    2016-09-01

    Full Text Available Microorganisms play a crucial role in the sustainability of the various ecosystems. The characterization of various interactions between microorganisms and other biotic factors is a necessary footstep to understand the association and functions of microbial communities. Among the different microbial interactions in an ecosystem, plant-microbe interaction plays an important role to balance the ecosystem. The present review explores plant microbe interactions using gene editing and system biology tools towards the comprehension in improvement of plant traits. Further, system biology tools like FBA, OptKnock and constrain based modeling helps in understanding such interactions as a whole. In addition, various gene editing tools have been summarized and a strategy has been hypothesized for the development of disease free plants. Furthermore, we have tried to summarize the predictions through data retrieved from various types of sources such as high throughput sequencing data (e.g. single nucleotide polymorphism (SNP detection, RNA-seq, proteomics and metabolic models have been reconstructed from such sequences for species communities. It is well known fact that systems biology approaches and modeling of biological networks will enable us to learn the insight of such network and will also help further in understanding these interactions.

  1. Convergent Inquiry in Science & Engineering: The Use of Atomic Force Microscopy in a Biology Class

    Science.gov (United States)

    Lee, Il-Sun; Byeon, Jung-Ho; Kwon, Yong-Ju

    2013-01-01

    The purpose of this study was to design a teaching method suitable for science high school students using atomic force microscopy. During their scientific inquiry procedure, high school students observed a micro-nanostructure of a biological sample, which is unobservable via an optical microscope. The developed teaching method enhanced students'…

  2. Molecular Cloning Designer Simulator (MCDS): All-in-one molecular cloning and genetic engineering design, simulation and management software for complex synthetic biology and metabolic engineering projects.

    Science.gov (United States)

    Shi, Zhenyu; Vickers, Claudia E

    2016-12-01

    Molecular Cloning Designer Simulator (MCDS) is a powerful new all-in-one cloning and genetic engineering design, simulation and management software platform developed for complex synthetic biology and metabolic engineering projects. In addition to standard functions, it has a number of features that are either unique, or are not found in combination in any one software package: (1) it has a novel interactive flow-chart user interface for complex multi-step processes, allowing an integrated overview of the whole project; (2) it can perform a user-defined workflow of cloning steps in a single execution of the software; (3) it can handle multiple types of genetic recombineering, a technique that is rapidly replacing classical cloning for many applications; (4) it includes experimental information to conveniently guide wet lab work; and (5) it can store results and comments to allow the tracking and management of the whole project in one platform. MCDS is freely available from https://mcds.codeplex.com.

  3. Development of a broad-host synthetic biology toolbox for Ralstonia eutropha and its application to engineering hydrocarbon biofuel production.

    Science.gov (United States)

    Bi, Changhao; Su, Peter; Müller, Jana; Yeh, Yi-Chun; Chhabra, Swapnil R; Beller, Harry R; Singer, Steven W; Hillson, Nathan J

    2013-11-13

    The chemoautotrophic bacterium Ralstonia eutropha can utilize H2/CO2 for growth under aerobic conditions. While this microbial host has great potential to be engineered to produce desired compounds (beyond polyhydroxybutyrate) directly from CO2, little work has been done to develop genetic part libraries to enable such endeavors. We report the development of a toolbox for the metabolic engineering of Ralstonia eutropha H16. We have constructed a set of broad-host-range plasmids bearing a variety of origins of replication, promoters, 5' mRNA stem-loop structures, and ribosomal binding sites. Specifically, we analyzed the origins of replication pCM62 (IncP), pBBR1, pKT (IncQ), and their variants. We tested the promoters P(BAD), T7, P(xyls/PM), P(lacUV5), and variants thereof for inducible expression. We also evaluated a T7 mRNA stem-loop structure sequence and compared a set of ribosomal binding site (RBS) sequences derived from Escherichia coli, R. eutropha, and a computational RBS design tool. Finally, we employed the toolbox to optimize hydrocarbon production in R. eutropha and demonstrated a 6-fold titer improvement using the appropriate combination of parts. We constructed and evaluated a versatile synthetic biology toolbox for Ralstonia eutropha metabolic engineering that could apply to other microbial hosts as well.

  4. Computation: A New Open Access Journal of Computational Chemistry, Computational Biology and Computational Engineering

    Directory of Open Access Journals (Sweden)

    Karlheinz Schwarz

    2013-09-01

    Full Text Available Computation (ISSN 2079-3197; http://www.mdpi.com/journal/computation is an international scientific open access journal focusing on fundamental work in the field of computational science and engineering. Computational science has become essential in many research areas by contributing to solving complex problems in fundamental science all the way to engineering. The very broad range of application domains suggests structuring this journal into three sections, which are briefly characterized below. In each section a further focusing will be provided by occasionally organizing special issues on topics of high interests, collecting papers on fundamental work in the field. More applied papers should be submitted to their corresponding specialist journals. To help us achieve our goal with this journal, we have an excellent editorial board to advise us on the exciting current and future trends in computation from methodology to application. We very much look forward to hearing all about the research going on across the world. [...

  5. Metabolic Engineering for Production of Biorenewable Fuels and Chemicals: Contributions of Synthetic Biology

    OpenAIRE

    Jarboe, Laura R.; Zhang, Xueli; Wang, Xuan; Moore, Jonathan C.; Shanmugam, K. T.; Ingram, Lonnie O.

    2010-01-01

    Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibito...

  6. The Integration of Nanotechnology and Biology for Cell Engineering: Promises and Challenges

    OpenAIRE

    Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2013-01-01

    Introduction: Successful tissue engineering strategies leading to the regeneration of a tissue depend on many factors, starting from the choice of appropriate scaffold material, tailoring the surface functionalities and topography, providing the correct amount of chemical and mechanical stimuli at the appropriate time points, and ensuring the uniform and precise localization of cells. Further challenges arise when more than one cell type has to be employed for the effective regeneration of an...

  7. Towards biologically relevant synthetic designer matrices in 3D bioprinting for tissue engineering and regenerative medicine

    KAUST Repository

    Costa, Rú ben M.; Rauf, Sakandar; Hauser, Charlotte

    2017-01-01

    3D bioprinting is one of the most promising technologies in tissue engineering and regenerative medicine. As new printing techniques and bioinks are getting developed, new cellular constructs with high resolution and functionality arise. Different to bioinks of animal, algal or plant origin, synthesized bioinks are proposed as superior biomaterials because their characteristics are fully under control. In this review, we will highlight the potential of synthetic biomaterials to be used as bioinks in 3D bioprinting to produce functionally enhanced matrices.

  8. Biologically Active Polycaprolactone/Titanium Hybrid Electrospun Nanofibers for Hard Tissue Engineering

    DEFF Research Database (Denmark)

    Barakat, Nasser A. M.; Sheikh, Faheem A.; Al-Deyab, Salem S.

    2011-01-01

    In this study, a novel strategy to improve the bioactivity of polycaprolactone nanofibers is proposed. Incorporation of pure titanium nanoparticles into polycaprolactone nanofibers strongly enhances the precipitation of bone-like apatite materials when the doped nanofibers are soaked in a simulat...... nanofiber mats and the successful incorporation of the titanium nanoparticles make the prepared polycaprolactone nanofiber mat a proper candidate for the hard-tissue engineering applications....

  9. Design and development of modular DNA assembly tools for Multigene Engineering and Synthetic Biology in Plants

    OpenAIRE

    Sarrión Perdigones, Manuel Alejandro

    2014-01-01

    The post-genomics era has put at the disposal of modern plant breeders an endless list of genetic building blocks for the design of new biotechnological crops. After a first wave of single-gene transgenic with controversial public acceptance, genomic information and technology is paving the way for increasingly complex designs based in multiple gene engineering. Those designs aiming at the production of inexpensive health-promoting compounds are most likely to be welcomed by consumers. In thi...

  10. Towards biologically relevant synthetic designer matrices in 3D bioprinting for tissue engineering and regenerative medicine

    KAUST Repository

    Costa, Rúben M.

    2017-05-12

    3D bioprinting is one of the most promising technologies in tissue engineering and regenerative medicine. As new printing techniques and bioinks are getting developed, new cellular constructs with high resolution and functionality arise. Different to bioinks of animal, algal or plant origin, synthesized bioinks are proposed as superior biomaterials because their characteristics are fully under control. In this review, we will highlight the potential of synthetic biomaterials to be used as bioinks in 3D bioprinting to produce functionally enhanced matrices.

  11. Large-scale Wind Turbine Blade Redesign Based on Reverse Engineering%大型风能发电机组叶片反求再设计

    Institute of Scientific and Technical Information of China (English)

    陶庆; 孙文磊

    2015-01-01

    叶片的外形设计和翼型的选择等都能影响风机性能和产能效率。提出一种大型风能发电机组叶片反求再设计的原理和方法,通过对大型风能发电机组叶片反求测量、大型风能发电机组叶片逆向CAD建模,寻找几何特征,探索制约叶片形状的基本因素,确定叶片截面参数计算公式,利用所开发的叶片翼型自动生成系统,完成了叶片的再设计,并得到了实际应用。%The large⁃scale wind turbine blade contour design and the choice of wing section affect the wind turbine performance and energy efficiency. A redesign principle and method for large⁃scale wind turbine blade was presented which was based on the analy⁃sis of blade CAD model from reverse engineering, looking for geometric features, exploring basic constraint factors on blade shape, and determining parameters of blade cross section calculation formula. Blade design was completed using this self⁃developed blade aerofoil automatic generation system. The results show that the redesign meets the production requirements.

  12. Reverse engineering of mandible and prosthetic framework: Effect of titanium implants in conjunction with titanium milled full arch bridge prostheses on the biomechanics of the mandible.

    Science.gov (United States)

    De Santis, Roberto; Gloria, Antonio; Russo, Teresa; D'Amora, Ugo; Varriale, Angelo; Veltri, Mario; Balleri, Piero; Mollica, Francesco; Riccitiello, Francesco; Ambrosio, Luigi

    2014-12-18

    This study aimed at investigating the effects of titanium implants and different configurations of full-arch prostheses on the biomechanics of edentulous mandibles. Reverse engineered, composite, anisotropic, edentulous mandibles made of a poly(methylmethacrylate) core and a glass fibre reinforced outer shell were rapid prototyped and instrumented with strain gauges. Brånemark implants RP platforms in conjunction with titanium Procera one-piece or two-piece bridges were used to simulate oral rehabilitations. A lateral load through the gonion regions was used to test the biomechanical effects of the rehabilitations. In addition, strains due to misfit of the one-piece titanium bridge were compared to those produced by one-piece cast gold bridges. Milled titanium bridges had a better fit than cast gold bridges. The stress distribution in mandibular bone rehabilitated with a one-piece bridge was more perturbed than that observed with a two-piece bridge. In particular the former induced a stress concentration and stress shielding in the molar and symphysis regions, while for the latter design these stresses were strongly reduced. In conclusion, prosthetic frameworks changed the biomechanics of the mandible as a result of both their design and manufacturing technology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering.

    Science.gov (United States)

    Menolascina, Filippo; Bellomo, Domenico; Maiwald, Thomas; Bevilacqua, Vitoantonio; Ciminelli, Caterina; Paradiso, Angelo; Tommasi, Stefania

    2009-10-15

    Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design strategy based on evolutionary algorithm to cope with the problem of information gathering in Systems Biology. On the basis of the theoretical results obtained in the field of control systems theory, we have studied the dynamical properties of the signals to be used in cell stimulation. The results of this study have been used to develop a microfluidic device for the automation of the process of cell stimulation for system identification. We have applied the proposed approach to the Epidermal Growth Factor Receptor pathway and we observed that it minimises the amount of parametric uncertainty associated to the identified model. A statistical framework based on Monte-Carlo estimations of the uncertainty ellipsoid confirmed the superiority of optimally designed experiments over canonical inputs. The proposed approach can be easily extended to multiobjective formulations that can also take advantage of identifiability analysis. Moreover, the availability of fully automated

  14. Optical coherence tomography: technology and applications (biological and medical physics, biomedical engineering)

    CERN Document Server

    2013-01-01

    Optical coherence tomography (OCT) is the optical analog of ultrasound imaging and is emerging as a powerful imaging technique that enables non-invasive, in vivo, high resolution, cross-sectional imaging in biological tissue. This book introduces OCT technology and applications not only from an optical and technological viewpoint, but also from biomedical and clinical perspectives. The chapters are written by leading research groups, in a style comprehensible to a broad audience.

  15. Reverse Osmosis

    Indian Academy of Sciences (India)

    many applications, one of which is desalination of seawater. The inaugural Nobel Prize in Chemistry was awarded in 1901 to van 't Hoff for his seminal work in this area. The present article explains the principle of osmosis and reverse osmosis. Osmosis and Reverse Osmosis. As the name suggests, reverse osmosis is the ...

  16. Microstructured surfaces engineered using biological templates: a facile approach for the fabrication of superhydrophobic surfaces

    Directory of Open Access Journals (Sweden)

    DUSAN LOSIC

    2008-10-01

    Full Text Available The fabrication of microstructured surfaces using biological templates was investigated with the aim of exploring of a facile and low cost approach for the fabrication of structured surfaces with superhydrophobic properties. Two soft lithographic techniques, i.e., replica moulding and nano-imprinting, were used to replicate the surfaces of a biological substrate. Leaves of the Agave plant (Agave attenuate, a cost-free biological template, were used as a model of a biosurface with superhydrophobic properties. The replication process was performed using two polymers: an elastomeric polymer, poly(dimethylsiloxane (PDMS, and a polyurethane (PU based, UV-curable polymer (NOA 60. In the first replication step, negative polymer replicas of the surface of leaves were fabricated, which were used as masters to fabricate positive polymer replicas by moulding and soft imprinting. The pattern with micro and nanostructures of the surface of the leaf possesses superhydrophobic properties, which was successfully replicated into both polymers. Finally, the positive replicas were coated with a thin gold film and modified with self-assembled monolayers (SAMs to verify the importance of the surface chemistry on the hydrophobic properties of the fabricated structures. Wetting (contact angle and structural (light microscopy and scanning electron microscopy characterisation was performed to confirm the hydrophobic properties of the fabricated surfaces (> 150°, as well as the precision and reproducibility of the replication process.

  17. A Novel Application of Synthetic Biology and Directed Evolution to Engineer Phage-based Antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Meiye [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2014-09-01

    The emergence of multiple drug resistant bacteria poses threats to human health, agriculture and food safety. Annually over 100,000 deaths and up to $20 billion loss to the U.S. economy are attributed to multiple drug resistant bacteria. With only four new chemical antibiotics in the drug development pipeline, we are in dire need of new solutions to address the emerging threat of multiple drug resistance. We propose a paradigm-changing approach to address the multi-drug resistant bacteria problem by utilizing Synthetic Biology (SynBio) methodologies to create and evolve “designer” bacteriophages or phages – viruses that specifically infect bacteria – to infect and kill newly emerging pathogenic bacterial strains WITHOUT the need for chemical antibiotics. A major advantage of using phage to combat pathogenic bacteria is that phages can co-evolve with their bacterial host, and Sandia can be the first in the world to establish an industrial scale Synthetic Biology pipeline for phage directed evolution for safe, targeted, customizable solution to bacterial drug resistance. Since there is no existing phage directed evolution effort within or outside of Sandia, this proposal is suitable as a high-risk LDRD effort to create the first pipeline for such an endeavor. The high potential reward nature of this proposal will be the immediate impact in decontamination and restoration of surfaces and infrastructure, with longer term impact in human or animal therapeutics. The synthetic biology and screening approaches will lead to fundamental knowledge of phage/bacteria co-evolution, making Sandia a world leader in directed evolution of bacteriophages.

  18. Science and engineering of nanodiamond particle surfaces for biological applications (Review).

    Science.gov (United States)

    Shenderova, Olga A; McGuire, Gary E

    2015-09-05

    Diamond has outstanding bulk properties such as super hardness, chemical inertness, biocompatibility, luminescence, to name just a few. In the nanoworld, in order to exploit these outstanding bulk properties, the surfaces of nanodiamond (ND) particles must be accordingly engineered for specific applications. Modification of functional groups on the ND's surface and the corresponding electrostatic properties determine their colloidal stability in solvents, formation of photonic crystals, controlled adsorption and release of cargo molecules, conjugation with biomolecules and polymers, and cellular uptake. The optical activity of the luminescent color centers in NDs depends on their proximity to the ND's surface and surface termination. In order to engineer the ND surface, a fundamental understanding of the specific structural features and sp(3)-sp(2) phase transformations on the surface of ND particles is required. In the case of ND particles produced by detonation of carbon containing explosives (detonation ND), it should also be taken into account that its structure depends on the synthesis parameters and subsequent processing. Thus, for development of a strategy of surface modification of detonation ND, it is imperative to know details of its production. In this review, the authors discuss ND particles structure, strategies for surface modification, electrokinetic properties of NDs in suspensions, and conclude with a brief overview of the relevant bioapplications.

  19. Smart Polymeric Hydrogels for Cartilage Tissue Engineering: A Review on the Chemistry and Biological Functions.

    Science.gov (United States)

    Eslahi, Niloofar; Abdorahim, Marjan; Simchi, Abdolreza

    2016-11-14

    Stimuli responsive hydrogels (SRHs) are attractive bioscaffolds for tissue engineering. The structural similarity of SRHs to the extracellular matrix (ECM) of many tissues offers great advantages for a minimally invasive tissue repair. Among various potential applications of SRHs, cartilage regeneration has attracted significant attention. The repair of cartilage damage is challenging in orthopedics owing to its low repair capacity. Recent advances include development of injectable hydrogels to minimize invasive surgery with nanostructured features and rapid stimuli-responsive characteristics. Nanostructured SRHs with more structural similarity to natural ECM up-regulate cell-material interactions for faster tissue repair and more controlled stimuli-response to environmental changes. This review highlights most recent advances in the development of nanostructured or smart hydrogels for cartilage tissue engineering. Different types of stimuli-responsive hydrogels are introduced and their fabrication processes through physicochemical procedures are reported. The applications and characteristics of natural and synthetic polymers used in SRHs are also reviewed with an outline on clinical considerations and challenges.

  20. Fiscal 1999 achievement report on regional consortium research and development project. Regional consortium activity in its 3rd year (Research and development of reverse engineering system for local craftwork articles); 1999 nendo chiiki kogeihin muke reverse engineering system no kenkyu kaihatsu seika hokokusho. 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-03-01

    The effort concerns Ryukyu craftwork articles. Reverse engineering used to be regarded as a technique of imitation or duplication but today it is drawing attention as a concept of positively utilizing the directionality of information flow in the integrated environment. In the development of a reverse information system, novel designs are created by utilizing a 3-dimensional data base, a high-efficiency fabrication technology for metal patterns for the press-molding of glass is established incorporating some fabrication diagnosing techniques, and a system is constructed under which fabrication accuracy is evaluated and difference data are fed back. In the development of technologies for metal pattern cutting and surface reforming, a metal pattern fabrication technology for molding glass, low in cost and high in performance, is systematized, which enables short delivery. In the diversification of glass products, Ryukyu patterns are collected and Ryukyu glass products are tentatively manufactured by press-molding, and a good result is achieved. In the field of total system technology, basic technologies for an advanced and integrated common production base are established. A virtual reality assisted designing system is developed, under which the designer feels force on the finger tips when preparing a shape for a 3-dimensional structure. (NEDO)

  1. Engineering of Soil Biological Quality from Nickel Mining Stockpile Using Two Earthworm Ecological Groups

    Directory of Open Access Journals (Sweden)

    L M H Kilowasid

    2015-04-01

    Full Text Available Earthworms have the ability in modifying soil biological quality for plant growth. Their ability is mostly depending on its ecological groups. The objectives of the research were to study the influence of two ecological groups of earthworms on soil microbial activity and soil micro-fauna abundance, and to know the potential of soil modified by earthworms as plant growth medium. Eight combination of individual earthworm from epigeic and endogeic groups was applied into pot that was filled by soil from two years of nickel stockpile and each treatment was repeated by five times. The experiment was following complete randomize design procedure. After sixteen days of research, the soil sample from each pot was analyzed for soil FDA activity, number of flagellate and nematodes. Furthermore, one kg of the soil from each pot was taken and every pot was grown by Paraserianthes falcataria seedling with the age of five days and continued its growth for two months. The results indicated that the soil FDA activity, number of flagellate and nematodes among treatments were significantly differences. In addition, it indicated the significant differences in dry weight of shoot, root, total plant, and root to shoot ratio of P. falcataria seedlings. It concluded that the combination of an individual number of epigeic and endogeic earthworms improved soil biological quality of stock pile, amd most suitable for seedlings growth in nickel mining area.

  2. Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors.

    Science.gov (United States)

    Ham, Stephanie L; Joshi, Ramila; Luker, Gary D; Tavana, Hossein

    2016-11-01

    Solid tumors develop as 3D tissue constructs. As tumors grow larger, spatial gradients of nutrients and oxygen and inadequate diffusive supply to cells distant from vasculature develops. Hypoxia initiates signaling and transcriptional alterations to promote survival of cancer cells and generation of cancer stem cells (CSCs) that have self-renewal and tumor-initiation capabilities. Both hypoxia and CSCs are associated with resistance to therapies and tumor relapse. This study demonstrates that 3D cancer cell models, known as tumor spheroids, generated with a polymeric aqueous two-phase system (ATPS) technology capture these important biological processes. Similar to solid tumors, spheroids of triple negative breast cancer cells deposit major extracellular matrix proteins. The molecular analysis establishes presence of hypoxic cells in the core region and expression of CSC gene and protein markers including CD24, CD133, and Nanog. Importantly, these spheroids resist treatment with chemotherapy drugs. A combination treatment approach using a hypoxia-activated prodrug, TH-302, and a chemotherapy drug, doxorubicin, successfully targets drug resistant spheroids. This study demonstrates that ATPS spheroids recapitulate important biological and functional properties of solid tumors and provide a unique model for studies in cancer research. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The EBI search engine: EBI search as a service-making biological data accessible for all.

    Science.gov (United States)

    Park, Young M; Squizzato, Silvano; Buso, Nicola; Gur, Tamer; Lopez, Rodrigo

    2017-07-03

    We present an update of the EBI Search engine, an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types that include nucleotide and protein sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, as well as the life science literature. EBI Search provides a powerful RESTful API that enables its integration into third-party portals, thus providing 'Search as a Service' capabilities, which are the main topic of this article. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. The EBI search engine: EBI search as a service—making biological data accessible for all

    Science.gov (United States)

    Park, Young M.; Squizzato, Silvano; Buso, Nicola; Gur, Tamer

    2017-01-01

    Abstract We present an update of the EBI Search engine, an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. The interconnectivity that exists between data resources at EMBL–EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types that include nucleotide and protein sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, as well as the life science literature. EBI Search provides a powerful RESTful API that enables its integration into third-party portals, thus providing ‘Search as a Service’ capabilities, which are the main topic of this article. PMID:28472374

  5. Expanding beyond canonical metabolism: Interfacing alternative elements, synthetic biology, and metabolic engineering

    Directory of Open Access Journals (Sweden)

    Kevin B. Reed

    2018-03-01

    Full Text Available Metabolic engineering offers an exquisite capacity to produce new molecules in a renewable manner. However, most industrial applications have focused on only a small subset of elements from the periodic table, centered around carbon biochemistry. This review aims to illustrate the expanse of chemical elements that can currently (and potentially be integrated into useful products using cellular systems. Specifically, we describe recent advances in expanding the cellular scope to include the halogens, selenium and the metalloids, and a variety of metal incorporations. These examples range from small molecules, heteroatom-linked uncommon elements, and natural products to biomining and nanotechnology applications. Collectively, this review covers the promise of an expanded range of elemental incorporations and the future impacts it may have on biotechnology.

  6. Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology.

    Science.gov (United States)

    Gill, Bartley J; West, Jennifer L

    2014-06-27

    Cancer progression is mediated by complex epigenetic, protein and structural influences. Critical among them are the biochemical, mechanical and architectural properties of the extracellular matrix (ECM). In recognition of the ECM's important role, cancer biologists have repurposed matrix mimetic culture systems first widely used by tissue engineers as new tools for in vitro study of tumor models. In this review we discuss the pathological changes in tumor ECM, the limitations of 2D culture on both traditional and polyacrylamide hydrogel surfaces in modeling these characteristics and advances in both naturally derived and synthetic scaffolds to facilitate more complex and controllable 3D cancer cell culture. Studies using naturally derived matrix materials like Matrigel and collagen have produced significant findings related to tumor morphogenesis and matrix invasion in a 3D environment and the mechanotransductive signaling that mediates key tumor-matrix interaction. However, lack of precise experimental control over important matrix factors in these matrices have increasingly led investigators to synthetic and semi-synthetic scaffolds that offer the engineering of specific ECM cues and the potential for more advanced experimental manipulations. Synthetic scaffolds composed of poly(ethylene glycol) (PEG), for example, facilitate highly biocompatible 3D culture, modular bioactive features like cell-mediated matrix degradation and complete independent control over matrix bioactivity and mechanics. Future work in PEG or similar reductionist synthetic matrix systems should enable the study of increasingly complex and dynamic tumor-ECM relationships in the hopes that accurate modeling of these relationships may reveal new cancer therapeutics targeting tumor progression and metastasis. © 2013 Published by Elsevier Ltd.

  7. MODEL-DRIVEN REVERSE ENGINEERING AND PROGRAM COMPREHENSION: AN EXAMPLE INGENIERÍA REVERSA Y COMPRENSIÓN DE PROGRAMAS DIRIGIDA POR MODELOS: UN EJEMPLO

    Directory of Open Access Journals (Sweden)

    Eugenio G Scalise P

    2010-04-01

    Full Text Available This paper presents an example of how Model-Driven Engineering (MDE can be applied to the development of tools for reverse engineering and program comprehension. The tool CodeCrawler was selected as an example; in particular, the polymetric view feature was computed using MDE techniques. To this end, two metamodels were proposed (source and target and meta-level transformations that were used to deduce the information of a polymetric view associated to any software project (source code. The technologies selected to develop the example were those related with the Eclipse Modeling Project, specifically the ATL and the KM3 languages. The approach used in this paper to obtain the implementation can be used to develop all the features of a MDE-oriented software comprehension tool, obtaining a domain-oriented implementation.En este artículo se presenta un ejemplo que describe cómo la Ingeniería Dirigida por Modelos (IDM puede ser aplicada al desarrollo de herramientas para la ingeniería reversa y comprensión de programas. Se seleccionó como caso de estudio la herramienta CodeCrawler, específicamente la funcionalidad denominada polymetric view, desarrollada mediante tecnologías y técnicas de la IDM. Para ello, se emplearon dos metamodelos (entrada y salida y transformaciones a nivel de los metamodelos que permiten generar la información de un polymetric view asociado a un proyecto de software, utilizando la información extraída del código fuente. Las tecnologías utilizadas para el desarrollo del ejemplo, las relacionadas con el Eclipse Modeling Project, específicamente el lenguaje de transformación ATL y el lenguaje KM3. El enfoque seguido para obtener la implementación resultante puede ser utilizado para desarrollar una herramienta de ingeniería reversa y comprensión de software mediante técnicas de la IDM, incorporando el vocabulario del dominio en la implementación.

  8. An engineered bacterium auxotrophic for an unnatural amino acid: a novel biological containment system

    Directory of Open Access Journals (Sweden)

    Yusuke Kato

    2015-09-01

    Full Text Available Biological containment is a genetic technique that programs dangerous organisms to grow only in the laboratory and to die in the natural environment. Auxotrophy for a substance not found in the natural environment is an ideal biological containment. Here, we constructed an Escherichia coli strain that cannot survive in the absence of the unnatural amino acid 3-iodo-L-tyrosine. This synthetic auxotrophy was achieved by conditional production of the antidote protein against the highly toxic enzyme colicin E3. An amber stop codon was inserted in the antidote gene. The translation of the antidote mRNA was controlled by a translational switch using amber-specific 3-iodo-L-tyrosine incorporation. The antidote is synthesized only when 3-iodo-L-tyrosine is present in the culture medium. The viability of this strain rapidly decreased with less than a 1 h half-life after removal of 3-iodo-L-tyrosine, suggesting that the decay of the antidote causes the host killing by activated colicin E3 in the absence of this unnatural amino acid. The contained strain grew 1.5 times more slowly than the parent strains. The escaper frequency was estimated to be 1.4 mutations (95% highest posterior density 1.1–1.8 per 105 cell divisions. This containment system can be constructed by only plasmid introduction without genome editing, suggesting that this system may be applicable to other microbes carrying toxin-antidote systems similar to that of colicin E3.

  9. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    Chengdong Xiong

    2009-07-01

    Full Text Available Abstract In this study, we report the physico-chemical and biological properties of a novel biodegradable composite scaffold made of nano-hydroxyapatite and natural derived polymers of chitosan and carboxymethyl cellulose, namely, n-HA/CS/CMC, which was prepared by freeze-drying method. The physico-chemical properties of n-HA/CS/CMC scaffold were tested by infrared absorption spectra (IR, transmission electron microscope(TEM, scanning electron microscope(SEM, universal material testing machine and phosphate buffer solution (PBS soaking experiment. Besides, the biological properties were evaluated by MG63 cells and Mesenchymal stem cells (MSCs culture experiment in vitro and a short period implantation study in vivo. The results show that the composite scaffold is mainly formed through the ionic crossing-linking of the two polyions between CS and CMC, and n-HA is incorporated into the polyelectrolyte matrix of CS-CMC without agglomeration, which endows the scaffold with good physico-chemical properties such as highly interconnected porous structure, high compressive strength and good structural stability and degradation. More important, the results of cells attached, proliferated on the scaffold indicate that the scaffold is non-toxic and has good cell biocompatibility, and the results of implantation experiment in vivo further confirm that the scaffold has good tissue biocompatibility. All the above results suggest that the novel degradable n-HA/CS/CMC composite scaffold has a great potential to be used as bone tissue engineering material.

  10. Preparation and biological properties of a novel composite scaffold of nano-hydroxyapatite/chitosan/carboxymethyl cellulose for bone tissue engineering

    Science.gov (United States)

    Liuyun, Jiang; Yubao, Li; Chengdong, Xiong

    2009-01-01

    In this study, we report the physico-chemical and biological properties of a novel biodegradable composite scaffold made of nano-hydroxyapatite and natural derived polymers of chitosan and carboxymethyl cellulose, namely, n-HA/CS/CMC, which was prepared by freeze-drying method. The physico-chemical properties of n-HA/CS/CMC scaffold were tested by infrared absorption spectra (IR), transmission electron microscope(TEM), scanning electron microscope(SEM), universal material testing machine and phosphate buffer solution (PBS) soaking experiment. Besides, the biological properties were evaluated by MG63 cells and Mesenchymal stem cells (MSCs) culture experiment in vitro and a short period implantation study in vivo. The results show that the composite scaffold is mainly formed through the ionic crossing-linking of the two polyions between CS and CMC, and n-HA is incorporated into the polyelectrolyte matrix of CS-CMC without agglomeration, which endows the scaffold with good physico-chemical properties such as highly interconnected porous structure, high compressive strength and good structural stability and degradation. More important, the results of cells attached, proliferated on the scaffold indicate that the scaffold is non-toxic and has good cell biocompatibility, and the results of implantation experiment in vivo further confirm that the scaffold has good tissue biocompatibility. All the above results suggest that the novel degradable n-HA/CS/CMC composite scaffold has a great potential to be used as bone tissue engineering material. PMID:19594953

  11. Characterization of mechanical and biological properties of 3-D scaffolds reinforced with zinc oxide for bone tissue engineering.

    Directory of Open Access Journals (Sweden)

    Pei Feng

    Full Text Available A scaffold for bone tissue engineering should have highly interconnected porous structure, appropriate mechanical and biological properties. In this work, we fabricated well-interconnected porous β-tricalcium phosphate (β-TCP scaffolds via selective laser sintering (SLS. We found that the mechanical and biological properties of the scaffolds were improved by doping of zinc oxide (ZnO. Our data showed that the fracture toughness increased from 1.09 to 1.40 MPam(1/2, and the compressive strength increased from 3.01 to 17.89 MPa when the content of ZnO increased from 0 to 2.5 wt%. It is hypothesized that the increase of ZnO would lead to a reduction in grain size and an increase in density of the strut. However, the fracture toughness and compressive strength decreased with further increasing of ZnO content, which may be due to the sharp increase in grain size. The biocompatibility of the scaffolds was investigated by analyzing the adhesion and the morphology of human osteoblast-like MG-63 cells cultured on the surfaces of the scaffolds. The scaffolds exhibited better and better ability to support cell attachment and proliferation when the content of ZnO increased from 0 to 2.5 wt%. Moreover, a bone like apatite layer formed on the surfaces of the scaffolds after incubation in simulated body fluid (SBF, indicating an ability of osteoinduction and osteoconduction. In summary, interconnected porous β-TCP scaffolds doped with ZnO were successfully fabricated and revealed good mechanical and biological properties, which may be used for bone repair and replacement potentially.

  12. Molecular biology of C4 phosphoenolpyruvate carboxylase: Structure, regulation and genetic engineering.

    Science.gov (United States)

    Rajagopalan, A V; Devi, M T; Raghavendra, A S

    1994-02-01

    Three to four families of nuclear genes encode different isoforms of phosphoenolpyruvate (PEP) carboxylase (PEPC): C4-specific, C3 or etiolated, CAM and root forms. C4 leaf PEPC is encoded by a single gene (ppc) in sorghum and maize, but multiple genes in the C4-dicot Flaveria trinervia. Selective expression of ppc in only C4-mesophyll cells is proposed to be due to nuclear factors, DNA methylation and a distinct gene promoter. Deduced amino acid sequences of C4-PEPC pinpoint the phosphorylatable serine near the N-terminus, C4-specific valine and serine residues near the C-terminus, conserved cysteine, lysine and histidine residues and PEP binding/catalytic sites. During the PEPC reaction, PEP and bicarbonate are first converted into carboxyphosphate and the enolate of pyruvate. Carboxyphosphate decomposes within the active site into Pi and CO2, the latter combining with the enolate to form oxalacetate. Besides carboxylation, PEPC catalyzes a HCO3 (-)-dependent hydrolysis of PEP to yield pyruvate and Pi. Post-translational regulation of PEPC occurs by a phosphorylation/dephosphorylation cascade in vivo and by reversible enzyme oligomerization in vitro. The interrelation between phosphorylation and oligomerization of the enzyme is not clear. PEPC-protein kinase (PEPC-PK), the enzyme responsible for phosphorylation of PEPC, has been studied extensively while only limited information is available on the protein phosphatase 2A capable of dephosphorylating PEPC. The C4 ppc was cloned and expressed in Escherichia coli as well as tobacco. The transformed E. coli produced a functional/phosphorylatable C4 PEPC and the transgenic tobacco plants expressed both C3 and C4 isoforms. Site-directed mutagenesis of ppc indicates the importance of His(138), His(579) and Arg(587) in catalysis and/or substrate-binding by the E. coli enzyme, Ser(8) in the regulation of sorghum PEPC. Important areas for further research on C4 PEPC are: mechanism of transduction of light signal during

  13. Training mechanical engineering students to utilize biological inspiration during product development.

    Science.gov (United States)

    Bruck, Hugh A; Gershon, Alan L; Golden, Ira; Gupta, Satyandra K; Gyger, Lawrence S; Magrab, Edward B; Spranklin, Brent W

    2007-12-01

    The use of bio-inspiration for the development of new products and devices requires new educational tools for students consisting of appropriate design and manufacturing technologies, as well as curriculum. At the University of Maryland, new educational tools have been developed that introduce bio-inspired product realization to undergraduate mechanical engineering students. These tools include the development of a bio-inspired design repository, a concurrent fabrication and assembly manufacturing technology, a series of undergraduate curriculum modules and a new senior elective in the bio-inspired robotics area. This paper first presents an overview of the two new design and manufacturing technologies that enable students to realize bio-inspired products, and describes how these technologies are integrated into the undergraduate educational experience. Then, the undergraduate curriculum modules are presented, which provide students with the fundamental design and manufacturing principles needed to support bio-inspired product and device development. Finally, an elective bio-inspired robotics project course is present, which provides undergraduates with the opportunity to demonstrate the application of the knowledge acquired through the curriculum modules in their senior year using the new design and manufacturing technologies.

  14. Cell biology of sarcomeric protein engineering: disease modeling and therapeutic potential.

    Science.gov (United States)

    Thompson, Brian R; Metzger, Joseph M

    2014-09-01

    The cardiac sarcomere is the functional unit for myocyte contraction. Ordered arrays of sarcomeric proteins, held in stoichiometric balance with each other, respond to calcium to coordinate contraction and relaxation of the heart. Altered sarcomeric structure-function underlies the primary basis of disease in multiple acquired and inherited heart disease states. Hypertrophic and restrictive cardiomyopathies are caused by inherited mutations in sarcomeric genes and result in altered contractility. Ischemia-mediated acidosis directly alters sarcomere function resulting in decreased contractility. In this review, we highlight the use of acute genetic engineering of adult cardiac myocytes through stoichiometric replacement of sarcomeric proteins in these disease states with particular focus on cardiac troponin I. Stoichiometric replacement of disease causing mutations has been instrumental in defining the molecular mechanisms of hypertrophic and restrictive cardiomyopathy in a cellular context. In addition, taking advantage of stoichiometric replacement through gene therapy is discussed, highlighting the ischemia-resistant histidine-button, A164H cTnI. Stoichiometric replacement of sarcomeric proteins offers a potential gene therapy avenue to replace mutant proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize altered sarcomeric function in disease. © 2014 Wiley Periodicals, Inc.

  15. Metabolic Engineering of Yeast and Plants for the Production of the Biologically Active Hydroxystilbene, Resveratrol

    Science.gov (United States)

    Jeandet, Philippe; Delaunois, Bertrand; Aziz, Aziz; Donnez, David; Vasserot, Yann; Cordelier, Sylvain; Courot, Eric

    2012-01-01

    Resveratrol, a stilbenic compound deriving from the phenyalanine/polymalonate route, being stilbene synthase the last and key enzyme of this pathway, recently has become the focus of a number of studies in medicine and plant physiology. Increased demand for this molecule for nutraceutical, cosmetic and possibly pharmaceutic uses, makes its production a necessity. In this context, the use of biotechnology through recombinant microorganisms and plants is particularly promising. Interesting results can indeed arise from the potential of genetically modified microorganisms as an alternative mechanism for producing resveratrol. Strategies used to tailoring yeast as they do not possess the genes that encode for the resveratrol pathway, will be described. On the other hand, most interest has centered in recent years, on STS gene transfer experiments from various origins to the genome of numerous plants. This work also presents a comprehensive review on plant molecular engineering with the STS gene, resulting in disease resistance against microorganisms and the enhancement of the antioxidant activities of several fruits in transgenic lines. PMID:22654481

  16. GRASP/Ada: Graphical Representations of Algorithms, Structures, and Processes for Ada. The development of a program analysis environment for Ada: Reverse engineering tools for Ada, task 2, phase 3

    Science.gov (United States)

    Cross, James H., II

    1991-01-01

    The main objective is the investigation, formulation, and generation of graphical representations of algorithms, structures, and processes for Ada (GRASP/Ada). The presented task, in which various graphical representations that can be extracted or generated from source code are described and categorized, is focused on reverse engineering. The following subject areas are covered: the system model; control structure diagram generator; object oriented design diagram generator; user interface; and the GRASP library.

  17. Nitric oxide and nitrous oxide turnover in natural and engineered microbial communities: biological pathways, chemical reactions, and novel technologies

    Science.gov (United States)

    Schreiber, Frank; Wunderlin, Pascal; Udert, Kai M.; Wells, George F.

    2012-01-01

    Nitrous oxide (N2O) is an environmentally important atmospheric trace gas because it is an effective greenhouse gas and it leads to ozone depletion through photo-chemical nitric oxide (NO) production in the stratosphere. Mitigating its steady increase in atmospheric concentration requires an understanding of the mechanisms that lead to its formation in natural and engineered microbial communities. N2O is formed biologically from the oxidation of hydroxylamine (NH2OH) or the reduction of nitrite (NO−2) to NO and further to N2O. Our review of the biological pathways for N2O production shows that apparently all organisms and pathways known to be involved in the catabolic branch of microbial N-cycle have the potential to catalyze the reduction of NO−2 to NO and the further reduction of NO to N2O, while N2O formation from NH2OH is only performed by ammonia oxidizing bacteria (AOB). In addition to biological pathways, we review important chemical reactions that can lead to NO and N2O formation due to the reactivity of NO−2, NH2OH, and nitroxyl (HNO). Moreover, biological N2O formation is highly dynamic in response to N-imbalance imposed on a system. Thus, understanding NO formation and capturing the dynamics of NO and N2O build-up are key to understand mechanisms of N2O release. Here, we discuss novel technologies that allow experiments on NO and N2O formation at high temporal resolution, namely NO and N2O microelectrodes and the dynamic analysis of the isotopic signature of N2O with quantum cascade laser absorption spectroscopy (QCLAS). In addition, we introduce other techniques that use the isotopic composition of N2O to distinguish production pathways and findings that were made with emerging molecular techniques in complex environments. Finally, we discuss how a combination of the presented tools might help to address important open questions on pathways and controls of nitrogen flow through complex microbial communities that eventually lead to N2O build

  18. Nitric oxide and nitrous oxide turnover in natural and engineered microbial communities: biological pathways, chemical reactions and novel technologies

    Directory of Open Access Journals (Sweden)

    Frank eSchreiber

    2012-10-01

    Full Text Available Nitrous oxide (N2O is an environmentally important atmospheric trace gas because it is an effective greenhouse gas and it leads to ozone depletion through photo-chemical nitric oxide (NO production in the stratosphere. Mitigating its steady increase in atmospheric concentration requires an understanding of the mechanisms that lead to its formation in natural and engineered microbial communities. N2O is formed biologically from the oxidation of hydroxylamine (NH2OH or the reduction of nitrite (NO2- to NO and further to N2O. Our review of the biological pathways for N2O production shows that apparently all organisms and pathways known to be involved in the catabolic branch of microbial N-cycle have the potential to catalyze the reduction of NO2- to NO and the further reduction of NO to N2O, while N2O formation from NH2OH is only performed by ammonia oxidizing bacteria. In addition to biological pathways, we review important chemical reactions that can lead to NO and N2O formation due to the reactivity of NO2-, NH2OH and nitroxyl (HNO. Moreover, biological N2O formation is highly dynamic in response to N-imbalance imposed on a system. Thus, understanding NO formation and capturing the dynamics of NO and N2O build-up are key to understand mechanisms of N2O release. Here, we discuss novel technologies that allow experiments on NO and N2O formation at high temporal resolution, namely NO and N2O microelectrodes and the dynamic analysis of the isotopic signature of N2O with quantum cascade laser based absorption spectroscopy. In addition, we introduce other techniques that use the isotopic composition of N2O to distinguish production pathways and findings that were made with emerging molecular techniques in complex environments. Finally, we discuss how a combination of the presented tools might help to address important open questions on pathways and controls of nitrogen flow through complex microbial communities that eventually lead to N2O build-up.

  19. Anatomic Mesenchymal Stem Cell-Based Engineered Cartilage Constructs for Biologic Total Joint Replacement

    Science.gov (United States)

    Saxena, Vishal; Kim, Minwook; Keah, Niobra M.; Neuwirth, Alexander L.; Stoeckl, Brendan D.; Bickard, Kevin; Restle, David J.; Salowe, Rebecca; Wang, Margaret Ye; Steinberg, David R.

    2016-01-01

    larger constructs. Immunohistochemistry showed abundant collagen type II staining and little collagen type I staining. APS/TEMED crosslinking can be used to produce MSC-seeded HA-based neocartilage and can be used in combination with rapid prototyping techniques to generate anatomic MSC-seeded HA constructs for use in filling large and anatomically complex chondral defects or for biologic joint replacement. PMID:26871863

  20. Developmental engineering: a new paradigm for the design and manufacturing of cell-based products. Part II: from genes to networks: tissue engineering from the viewpoint of systems biology and network science.

    Science.gov (United States)

    Lenas, Petros; Moos, Malcolm; Luyten, Frank P

    2009-12-01

    The field of tissue engineering is moving toward a new concept of "in vitro biomimetics of in vivo tissue development." In Part I of this series, we proposed a theoretical framework integrating the concepts of developmental biology with those of process design to provide the rules for the design of biomimetic processes. We named this methodology "developmental engineering" to emphasize that it is not the tissue but the process of in vitro tissue development that has to be engineered. To formulate the process design rules in a rigorous way that will allow a computational design, we should refer to mathematical methods to model the biological process taking place in vitro. Tissue functions cannot be attributed to individual molecules but rather to complex interactions between the numerous components of a cell and interactions between cells in a tissue that form a network. For tissue engineering to advance to the level of a technologically driven discipline amenable to well-established principles of process engineering, a scientifically rigorous formulation is needed of the general design rules so that the behavior of networks of genes, proteins, or cells that govern the unfolding of developmental processes could be related to the design parameters. Now that sufficient experimental data exist to construct plausible mathematical models of many biological control circuits, explicit hypotheses can be evaluated using computational approaches to facilitate process design. Recent progress in systems biology has shown that the empirical concepts of developmental biology that we used in Part I to extract the rules of biomimetic process design can be expressed in rigorous mathematical terms. This allows the accurate characterization of manufacturing processes in tissue engineering as well as the properties of the artificial tissues themselves. In addition, network science has recently shown that the behavior of biological networks strongly depends on their topology and has

  1. Design and validation of a dynamic cell-culture system for bone biology research and exogenous tissue-engineering applications.

    Science.gov (United States)

    Allori, Alexander C; Davidson, Edward H; Reformat, Derek D; Sailon, Alexander M; Freeman, James; Vaughan, Adam; Wootton, David; Clark, Elizabeth; Ricci, John L; Warren, Stephen M

    2016-10-01

    Bone lacunocanalicular fluid flow ensures chemotransportation and provides a mechanical stimulus to cells. Traditional static cell-culture methods are ill-suited to study the intricacies of bone biology because they ignore the three-dimensionality of meaningful cellular networks and the lacunocanalicular system; furthermore, reliance on diffusion alone for nutrient supply and waste product removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow-perfusion system was custom-designed to overcome these limitations: eight adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured using a three-dimensional (3D) periodic microprinting process and were composed of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes, pore sizes and structural configurations. A multi-channel peristaltic pump drew medium from parallel reservoirs and perfused it through each scaffold at a programmable rate. Hermetically sealed valves permitted sampling or replacement of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected to withstand continuous perfusion for > 2 months without leakage. Computational modelling was performed to assess the adequacy of oxygen supply and the range of fluid shear stress in the bioreactor-scaffold system, using 12 × 6 mm scaffolds, and these models suggested scaffold design modifications that improved oxygen delivery while enhancing physiological shear stress. This system may prove useful in studying complex 3D bone biology and in developing strategies for engineering thick 3D bone constructs. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Doped tricalcium phosphate bone tissue engineering scaffolds using sucrose as template and microwave sintering: enhancement of mechanical and biological properties.

    Science.gov (United States)

    Ke, Dongxu; Bose, Susmita

    2017-09-01

    β-tricalcium phosphate (β-TCP) is a widely used biocompatible ceramic in orthopedic and dental applications. However, its osteoinductivity and mechanical properties still require improvements. In this study, porous β-TCP and MgO/ZnO-TCP scaffolds were prepared by the thermal decomposition of sucrose. Crack-free cylindrical scaffolds could only be prepared with the addition of MgO and ZnO due to their stabilization effects. Porous MgO/ZnO-TCP scaffolds with a density of 61.39±0.66%, an estimated pore size of 200μm and a compressive strength of 24.96±3.07MPa were prepared by using 25wt% sucrose after conventional sintering at 1250°C. Microwave sintering further increased the compressive strength to 37.94±6.70MPa, but it decreased the open interconnected porosity to 8.74±1.38%. In addition, the incorporation of polycaprolactone (PCL) increased 22.36±3.22% of toughness while maintaining its compressive strength at 25.45±2.21MPa. Human osteoblast cell line was seeded on scaffolds to evaluate the effects of MgO/ZnO and PCL on the biological property of β-TCP in vitro. Both MgO/ZnO and PCL improved osteoinductivity of β-TCP. PCL also decreased osteoblastic apoptosis due to its particular surface chemistry. This novel porous MgO/ZnO-TCP scaffold with PCL shows improved mechanical and biological properties, which has great potential in bone tissue engineering applications. Copyright © 2017. Published by Elsevier B.V.

  3. Thermomchromic Reaction-Induced Reversible Upconversion Emission Modulation for Switching Devices and Tunable Upconversion Emission Based on Defect Engineering of WO3:Yb3+,Er3+ Phosphor.

    Science.gov (United States)

    Ruan, Jiufeng; Yang, Zhengwen; Huang, Anjun; Zhang, Hailu; Qiu, Jianbei; Song, Zhiguo

    2018-05-02

    Reversible luminescence modulation of upconversion phosphors has the potential applications as photoswitches and optical memory and data storage devices. Previously, the photochromic reaction was extensively used for the realization of reversible luminescence modulation. It is very necessary to develop other approaches such as thermomchromic reaction to obtain the reversible upconversion luminescence modulation. In this work, the WO 3 :Yb 3+ ,Er 3+ phosphors with various colors were prepared at various temperatures, exhibiting tunable upconversion luminescence attributed to the formation of oxygen vacancies in the host. Upon heat treatment in the reducing atmosphere or air, the WO 3 :Yb 3+ ,Er 3+ phosphors show a reversible thermomchromic property. The reversible upconversion luminescence modulation of WO 3 :Yb 3+ ,Er 3+ phosphors was observed based on thermomchromic reaction. Additionally, the upconversion luminescence modulation is maintained after several cycles, indicating its excellent stability. The WO 3 :Yb 3+ ,Er 3+ phosphors with reversible upconversion luminescence and excellent reproducibility have potential applications as the photoswitches and optical memory and data storage devices.

  4. Efficacy of genetically engineered biological agents in the treatment of uveitis associated with rheumatic diseases in children

    Directory of Open Access Journals (Sweden)

    V V Neroyev

    2012-01-01

    Full Text Available The efficiency of incorporating genetically engineered biological agents (GEBAs into a combination treatment regimen for rheumatic diseases (RD (juvenile idiopathic arthritis, Behcet's disease in relation to associated uveitis of varying severity was studied in 92 children aged 2 to 17 years. The follow-up lasted 1.5 to 49 months. Twenty-three patients took consecutively 2 to 5 GEBAs. When infliximab was used, remission of uveitis occurred in 21% of 38 children and the disease activity and/or recurrence rates reduced in an additional 21%. These were in 45 and 38.6% of 44 patients on adalimumab (ADA and in 27.8 and 27.8% of 18 patients on abatacept, respectively. There was an association of the efficiency of therapy with the severity of uveitis at the start of treatment. The use of ADA induced a steady remission of panuveitis resistant to therapy with glucocorticoids and cyclosporine in both patients with Behcet's disease. One of 4 rituximab-treated patients achieved a steady remission. Tocilizumab therapy caused an exacerbation of uveitis in 1 patient. The postoperative period showed no inflammatory complications in most cases (37 operations, 26 eyes, 20 patients. No local adverse reactions were seen; systemic reactions occurred in 14% of the patients, this caused GEBAs to be discontinued in 7%. There is evidence for a need for further investigations into the efficacy of GEBAs in RD-associated uveitis in children in order to define success criteria, differentiated indications, and therapy regimens.

  5. The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears.

    Science.gov (United States)

    Rothrauff, Benjamin B; Pauyo, Thierry; Debski, Richard E; Rodosky, Mark W; Tuan, Rocky S; Musahl, Volker

    2017-08-01

    The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.

  6. Characterization of a multiculture in-vitro cell exposure chamber for assessing the biological impact of diesel engine exhaust

    International Nuclear Information System (INIS)

    Asimakopoulou, Akrivi; Daskalos, Manos; Chasapidis, Leonidas; Akritidis, Theofilaktos; Vlachos, Nickolaos D; Papaioannou, Eleni; Konstandopoulos, Athanasios G

    2011-01-01

    In order to study the various health influencing parameters related to particulate as well as to gas-phase pollutants emitted by Diesel engine exhaust, there is an urgent need for appropriate sampling devices and methods for cell exposure studies and associated biological and toxicological tests. In a previous paper [1], a specific concept for a cell culture exposure chamber was introduced to allow the uniform exposure of cell cultures to diesel aerosols. In the present work, this cell culture exposure chamber is evaluated and characterized with state-of-the-art nanoparticles measurement instrumentation to assess the local deposition of soot aggregates on the cell cultures and any losses due to particle deposition on the cell culture exposure chamber walls, and in addition an upgraded Multiculture Exposure Chamber (MEC) for in vitro continuous flow cell exposure tests is introduced with improved, compared to the previous version, features. Analysis and design of the MEC employs CFD and true to geometry representations of soot particle aggregates.

  7. Mechanical, Biological and Electrochemical Investigations of Advanced Micro/Nano Materials for Tissue Engineering and Energy Storage

    Science.gov (United States)

    Pu, Juan

    Various micro/nano materials have been extensively studied for applications in tissue engineering and energy storage. Tissue engineering seeks to repair or replace damaged tissue by integrating approaches from cellular/molecular biology and material chemistry/engineering. A major challenge is the consistent design of three-dimensional (3D) scaffolds that mimic the structure and biological functions of extracellular matrix (ECM), guide cell migration, provide mechanical support, and regulate cell activity. Electrospun micro/nanofibers have been investigated as promising tissue engineering scaffolds because they resemble native ECM and possess tunable surface morphologies. Supercapacitors, one of the energy storage devices, bridge the performance gap between rechargeable batteries and conventional capacitors. Active electrode materials of supercapacitors must possess high specific surface area, high conductivity, and good electrochemical properties. Carbon-based micro/nano-particles, such as graphene, activated carbon (AC), and carbon nanotubes, are commonly used as active electrode materials for storing charge in supercapacitors by the electrical double layer mechanism due to their high specific surface area and excellent conductivity. In this thesis, the mechanical properties of electrospun bilayer microfibrous membranes were investigated for potential applications in tissue engineering. Bilayer microfibrous membranes of poly(l-lactic acid) (PLLA) were fabricated by electrospinning using a parallel-disk mandrel configuration, which resulted in the sequential deposition of a layer with aligned fibers (AFL) across the two parallel disks and a layer with random fibers (RFL), both deposited by a single process step. The membrane structure and fiber alignment were characterized by scanning electron microscopy and two-dimensional fast Fourier transform. Because of the intricacies of the generated electric field, the bilayer membranes exhibited higher porosity than the

  8. Report of the results of the fiscal 1997 regional consortium R and D project. Regional consortium energy field / research and development of a reverse engineering system for local industrial articles (first fiscal year); 1997 nendo chiiki consortium kenkyu kaihatsu jigyo. Chiiki consortium bun`ya / chiiki kogeihin muke reverse engineering system no kenkyu kaihatsu (daiichi nendo) seika hokokusho

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    The paper described the fiscal 1997 result of the research on the application of local industrial article use reverse engineering (RE, it had been regarded as imitation and reproduction technology, but has recently been as a part of the production information integration). With the actual local industrial article as standard, which has features in design and was added with local traditionality, such as glass having 3D free-form surface, 3D shape information modeling technology RE is developed, and a system for direct automatic metal mold processing is established, aiming at shortening of delivery date, cost reduction and higher grade. The target of the research is Okinawa prefecture. In fiscal 1997, study was made of the speeding-up of the non-contact 3D shape information inputting (multi-point simultaneous inputting by CCD of the laser reflected light of the actual model) and the data storage technology. Cast iron was selected as molding materials, judging from reactivity/machinability with heat resistant glass. Also studied was the blend of glass materials suitable for press forming. Further, studies were proceeded with of development of intellectual cutting tools into which sensor function is integrated and of virtual reality for facilitating/accelerating the design up to metal mold manufacturing. 39 refs., 88 figs., 21 tabs.

  9. Identification of Cysteine Proteases and Screening of Cysteine Protease Inhibitors in Biological Samples by a Two-Dimensional Gel System of Zymography and Reverse Zymography

    OpenAIRE

    Saitoh, Eiichi; Yamamoto, Shinya; Okamoto, Eishiro; Hayakawa, Yoshimi; Hoshino, Takashi; Sato, Ritsuko; Isemura, Satoko; Ohtsubo, Sadami; Taniguchi, Masayuki

    2007-01-01

    We have developed a two-dimensional (2D-) gel system of zymography and reverse zymography for the detection and characterization of proteases and protease inhibitors. Isoelectric focusing (IEF) agarose gels with pH gradients were employed for separation in the fi rst-dimension and sodium dodecyl sulfate (SDS)-polyacrylamide gel copolymerized with gelatin used for the second dimension. Proteases and protease inhibitors separated by IEF gel were applied on the second gel without trichloroacetic...

  10. Reverse Ecology: from systems to environments and back.

    Science.gov (United States)

    Levy, Roie; Borenstein, Elhanan

    2012-01-01

    The structure of complex biological systems reflects not only their function but also the environments in which they evolved and are adapted to. Reverse Ecology-an emerging new frontier in Evolutionary Systems Biology-aims to extract this information and to obtain novel insights into an organism's ecology. The Reverse Ecology framework facilitates the translation of high-throughput genomic data into large-scale ecological data, and has the potential to transform ecology into a high-throughput field. In this chapter, we describe some of the pioneering work in Reverse Ecology, demonstrating how system-level analysis of complex biological networks can be used to predict the natural habitats of poorly characterized microbial species, their interactions with other species, and universal patterns governing the adaptation of organisms to their environments. We further present several studies that applied Reverse Ecology to elucidate various aspects of microbial ecology, and lay out exciting future directions and potential future applications in biotechnology, biomedicine, and ecological engineering.

  11. Biological effects of radiation

    International Nuclear Information System (INIS)

    2013-01-01

    This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

  12. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  13. Reverse Engineering and Software Products Reuse to Teach Collaborative Web Portals: A Case Study with Final-Year Computer Science Students

    Science.gov (United States)

    Medina-Dominguez, Fuensanta; Sanchez-Segura, Maria-Isabel; Mora-Soto, Arturo; Amescua, Antonio

    2010-01-01

    The development of collaborative Web applications does not follow a software engineering methodology. This is because when university students study Web applications in general, and collaborative Web portals in particular, they are not being trained in the use of software engineering techniques to develop collaborative Web portals. This paper…

  14. Distinct difference in relative biological effectiveness of 252Cf neutrons for the induction of mitotic crossing over and intragenic reversion of the white-ivory allele in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Yoshikawa, Isao; Hoshi, Masaharu; Ikenaga, Mituo

    1996-01-01

    The relative biological effectiveness (RBE) of 252 Cf neutrons was determined for two different types of somatic mutations, i.e., loss of heterozygosity for wing-hair mutations and reversion of the mutant white-ivory eye-color, in Drosophila melanogaster. Loss of heterozygosity for wing-hair mutations results predominantly from mitotic crossing over induced in wing anlage cells of larvae, while the reverse mutation of eye-color is due to an intragenic structural change in the white locus on the X-chromosome. For a quantitative comparison of RBE values for these events, we have constructed a combined mutation assay system so that induced mutant wing-hair clones as well as revertant eye-color clones can be detected simultaneously in the same individuals. Larvae were irradiated at the age of 80±4 h post-oviposition with 252 Cf neutrons or 137 Cs γ-rays, and male adult flies were examined under the microscope for the presence of the two types of clonal mosaic spots appearing. The induction of wing-hair spots per dose unit was much greater for 252 Cf neutrons than for 137 Cs γ -rays, whereas the frequencies of eye-color reversion were similar for neutrons and γ-rays. The estimated RBE values of neutrons were 8.5 and 1.2 for the induction of mutant wing-hair spots and revertant eye-color spots, respectively. These results indicate that the RBE of neutrons is much greater for mitotic crossing over in comparison to the intragenic white-ivory reversion events. Possible causes for the difference in RBE are discussed

  15. Synthesis, biological evaluation and molecular modeling of 2-Hydroxyisoquinoline-1,3-dione analogues as inhibitors of HIV reverse transcriptase associated ribonuclease H and polymerase.

    Science.gov (United States)

    Tang, Jing; Vernekar, Sanjeev Kumar V; Chen, Yue-Lei; Miller, Lena; Huber, Andrew D; Myshakina, Nataliya; Sarafianos, Stefan G; Parniak, Michael A; Wang, Zhengqiang

    2017-06-16

    Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function not clinically validated as an antiviral target. 2-Hydroxyisoquinoline-1,3-dione (HID) is known to confer active site directed inhibition of divalent metal-dependent enzymatic functions, such as HIV RNase H, integrase (IN) and hepatitis C virus (HCV) NS5B polymerase. We report herein the synthesis and biochemical evaluation of a few C-5, C-6 or C-7 substituted HID subtypes as HIV RNase H inhibitors. Our data indicate that while some of these subtypes inhibited both the RNase H and polymerase (pol) functions of RT, potent and selective RNase H inhibition was achieved with subtypes 8-9 as exemplified with compounds 8c and 9c. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. Evaluation of Biological Toxicity of CdTe Quantum Dots with Different Coating Reagents according to Protein Expression of Engineering Escherichia coli

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2015-01-01

    Full Text Available The results obtained from toxicity assessment of quantum dots (QDs can be used to establish guidelines for the application of QDs in bioimaging. This paper focused on the design of a novel method to evaluate the toxicity of CdTe QDs using engineering Escherichia coli as a model. The toxicity of mercaptoacetic acid (MPA, glutathione (GSH, and L-cysteine (Cys capped CdTe QDs was analyzed according to the heterologous protein expression in BL21/DE3, engineering Escherichia coli extensively used for protein expression. The results showed that the MPA-CdTe QDs had more serious toxicity than the other two kinds of CdTe QDs. The microscopic images and SEM micrographs further proved that both the proliferation and the protein expression of engineering Escherichia coli were inhibited after treatment with MPA-CdTe QDs. The proposed method is important to evaluate biological toxicity of both QDs and other nanoparticles.

  17. Synthesis of a mixed-model stationary phase derived from glutamine for HPLC separation of structurally different biologically active compounds: HILIC and reversed-phase applications.

    Science.gov (United States)

    Aral, Tarık; Aral, Hayriye; Ziyadanoğulları, Berrin; Ziyadanoğulları, Recep

    2015-01-01

    A novel mixed-mode stationary phase was synthesised starting from N-Boc-glutamine, aniline and spherical silica gel (4 µm, 60 Å). The prepared stationary phase was characterized by IR and elemental analysis. The new stationary phase bears an embedded amide group into phenyl ring, highly polar a terminal amide group and non-polar groups (phenyl and alkyl groups). At first, this new mixed-mode stationary phase was used for HILIC separation of four nucleotides and five nucleosides. The effects of different separation conditions, such as pH value, mobile phase and temperature, on the separation process were investigated. The optimum separation for nucleotides was achieved using HILIC isocratic elution with aqueous mobile phase and acetonitrile with 20°C column temperature. Under these conditions, the four nucleotides could be separated and detected at 265 nm within 14 min. Five nucleosides were separated under HILIC isocratic elution with aqueous mobile phase containing pH=3.25 phosphate buffer (10mM) and acetonitrile with 20°C column temperature and detected at 265 nm within 14 min. Chromatographic parameters as retention factor, selectivity, theoretical plate number and peak asymmetry factor were calculated for the effect of temperature and water content in mobile phase on the separation process. The new column was also tested for nucleotides and nucleosides mixture and six analytes were separated in 10min. The chromatographic behaviours of these polar analytes on the new mixed-model stationary phase were compared with those of HILIC columns under similar conditions. Further, phytohormones and phenolic compounds were separated in order to see influence of the new stationary phase in reverse phase conditions. Eleven plant phytohormones were separated within 13 min using RP-HPLC gradient elution with aqueous mobile phase containing pH=2.5 phosphate buffer (10mM) and acetonitrile with 20°C column temperature and detected at 230 or 278 nm. The best separation

  18. D-seco-Vitamin D analogs having reversed configurations at C-13 and C-14: Synthesis, docking studies and biological evaluation.

    Science.gov (United States)

    Szybinski, Marcin; Sokolowska, Katarzyna; Sicinski, Rafal R; Plum, Lori A; DeLuca, Hector F

    2017-10-01

    Prompted by results of molecular modeling performed on the seco-d-ring-vitamins D, we turned our attention to such analogs, having reversed configurations at C-13 and C-14, as the next goals of our studies on the structure-activity relationship for vitamin D compounds. First, we developed an efficient total synthesis of the "upper" C/seco-d-ring fragment with a 7-carbon side chain. Then, we coupled it with A-ring fragments using Sonogashira or Wittig-Horner protocol, providing the targeted D-seco analogs of 1α,25-dihydroxyvitamin D 3 and 1α,25-dihydroxy-19-norvitamin D 3 possessing a vinyl substituent at C-14 and a double bond between C-17 and C-20. The affinities of the synthesized vitamin D analogs to the full-length recombinant rat VDR were examined, as well as their differentiating and transcriptional activities. In these in vitro tests, they were significantly less active compared to 1α,25-(OH) 2 D 3 . Moreover, it was established that the analogs tested in vivo in rats showed no calcemic potency. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

    Science.gov (United States)

    Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

    2000-05-04

    Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  20. Reverse Osmosis

    Indian Academy of Sciences (India)

    Osmosis is a phenomenon which regulates many biological functions in plants and animals. That the plants stand upright, or the water reaches the tip of every leaf of a plant is due to osmotic pressure. The fact that we cannot survive by drinking seawater is also linked to this same phenomenon. J H van 't. Hoff showed in ...

  1. Engineering and Scaling the Spontaneous Magnetization Reversal of Faraday Induced Magnetic Relaxation in Nano-Sized Amorphous Ni Coated on Crystalline Au.

    Science.gov (United States)

    Li, Wen-Hsien; Lee, Chi-Hung; Kuo, Chen-Chen

    2016-05-28

    We report on the generation of large inverse remanent magnetizations in nano-sized core/shell structure of Au/Ni by turning off the applied magnetic field. The remanent magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before the switching off of the magnetic field. Spontaneous reversal in direction and increase in magnitude of the remanent magnetization in subsequent relaxations over time were found. All of the various types of temporal relaxation curves of the remanent magnetizations are successfully scaled by a stretched exponential decay profile, characterized by two pairs of relaxation times and dynamic exponents. The relaxation time is used to describe the reduction rate, while the dynamic exponent describes the dynamical slowing down of the relaxation through time evolution. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction.

  2. Engineering and Scaling the Spontaneous Magnetization Reversal of Faraday Induced Magnetic Relaxation in Nano-Sized Amorphous Ni Coated on Crystalline Au

    Science.gov (United States)

    Li, Wen-Hsien; Lee, Chi-Hung; Kuo, Chen-Chen

    2016-01-01

    We report on the generation of large inverse remanent magnetizations in nano-sized core/shell structure of Au/Ni by turning off the applied magnetic field. The remanent magnetization is very sensitive to the field reduction rate as well as to the thermal and field processes before the switching off of the magnetic field. Spontaneous reversal in direction and increase in magnitude of the remanent magnetization in subsequent relaxations over time were found. All of the various types of temporal relaxation curves of the remanent magnetizations are successfully scaled by a stretched exponential decay profile, characterized by two pairs of relaxation times and dynamic exponents. The relaxation time is used to describe the reduction rate, while the dynamic exponent describes the dynamical slowing down of the relaxation through time evolution. The key to these effects is to have the induced eddy current running beneath the amorphous Ni shells through Faraday induction. PMID:28773549

  3. Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.

    Science.gov (United States)

    Benedetti, Sara; Uno, Narumi; Hoshiya, Hidetoshi; Ragazzi, Martina; Ferrari, Giulia; Kazuki, Yasuhiro; Moyle, Louise Anne; Tonlorenzi, Rossana; Lombardo, Angelo; Chaouch, Soraya; Mouly, Vincent; Moore, Marc; Popplewell, Linda; Kazuki, Kanako; Katoh, Motonobu; Naldini, Luigi; Dickson, George; Messina, Graziella; Oshimura, Mitsuo; Cossu, Giulio; Tedesco, Francesco Saverio

    2018-02-01

    Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combination of large-capacity vectors, such as human artificial chromosomes (HACs), with stem/progenitor cells may overcome this limitation. We previously reported amelioration of the dystrophic phenotype in mice transplanted with murine muscle progenitors containing a HAC with the entire dystrophin locus (DYS-HAC). However, translation of this strategy to human muscle progenitors requires extension of their proliferative potential to withstand clonal cell expansion after HAC transfer. Here, we show that reversible cell immortalisation mediated by lentivirally delivered excisable hTERT and Bmi1 transgenes extended cell proliferation, enabling transfer of a novel DYS-HAC into DMD satellite cell-derived myoblasts and perivascular cell-derived mesoangioblasts. Genetically corrected cells maintained a stable karyotype, did not undergo tumorigenic transformation and retained their migration ability. Cells remained myogenic in vitro (spontaneously or upon MyoD induction) and engrafted murine skeletal muscle upon transplantation. Finally, we combined the aforementioned functions into a next-generation HAC capable of delivering reversible immortalisation, complete genetic correction, additional dystrophin expression, inducible differentiation and controllable cell death. This work establishes a novel platform for complex gene transfer into clinically relevant human muscle progenitors for DMD gene therapy. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  4. Hybrid chitosan-ß-glycerol phosphate-gelatin nano-/micro fibrous scaffolds with suitable mechanical and biological properties for tissue engineering.

    Science.gov (United States)

    Lotfi, Marzieh; Bagherzadeh, Roohollah; Naderi-Meshkin, Hojjat; Mahdipour, Elahe; Mafinezhad, Asghar; Sadeghnia, Hamid Reza; Esmaily, Habibollah; Maleki, Masoud; Hasssanzadeh, Halimeh; Ghayaour-Mobarhan, Majid; Bidkhori, Hamid Reza; Bahrami, Ahmad Reza

    2016-03-01

    Scaffold-based tissue engineering is considered as a promising approach in the regenerative medicine. Graft instability of collagen, by causing poor mechanical properties and rapid degradation, and their hard handling remains major challenges to be addressed. In this research, a composite structured nano-/microfibrous scaffold, made from a mixture of chitosan-ß-glycerol phosphate-gelatin (chitosan-GP-gelatin) using a standard electrospinning set-up was developed. Gelatin-acid acetic and chitosan ß-glycerol phosphate-HCL solutions were prepared at ratios of 30/70, 50/50, 70/30 (w/w) and their mechanical and biological properties were engineered. Furthermore, the pore structure of the fabricated nanofibrous scaffolds was investigated and predicted using a theoretical model. Higher gelatin concentrations in the polymer blend resulted in significant increase in mean pore size and its distribution. Interaction between the scaffold and the contained cells was also monitored and compared in the test and control groups. Scaffolds with higher chitosan concentrations showed higher rate of cell attachment with better proliferation property, compared with gelatin-only scaffolds. The fabricated scaffolds, unlike many other natural polymers, also exhibit non-toxic and biodegradable properties in the grafted tissues. In conclusion, the data clearly showed that the fabricated biomaterial is a biologically compatible scaffold with potential to serve as a proper platform for retaining the cultured cells for further application in cell-based tissue engineering, especially in wound healing practices. These results suggested the potential of using mesoporous composite chitosan-GP-gelatin fibrous scaffolds for engineering three-dimensional tissues with different inherent cell characteristics. © 2015 Wiley Periodicals, Inc.

  5. Building a Better Microreactor: Enzyme Catalysis in AOT/Bile Salt Reversed Micelles

    National Research Council Canada - National Science Library

    McGown, Linda

    2001-01-01

    .... We have shown that trihydroxy bile salts modify the interfacial properties of AOT reversed micelles, thereby affecting the reversed micellar structure, the biological activity of entrapped enzymes...

  6. Some Physical, Chemical, and Biological Parameters of Samples of Scleractinium Coral Aquaculture Skeleton Used for Reconstruction/Engineering of the Bone Tissue.

    Science.gov (United States)

    Popov, A A; Sergeeva, N S; Britaev, T A; Komlev, V S; Sviridova, I K; Kirsanova, V A; Akhmedova, S A; Dgebuadze, P Yu; Teterina, A Yu; Kuvshinova, E A; Schanskii, Ya D

    2015-08-01

    Physical and chemical (phase and chemical composition, dynamics of resorption, and strength properties), and biological (cytological compatibility and scaffold properties of the surface) properties of samples of scleractinium coral skeletons from aquacultures of three types and corresponding samples of natural coral skeletons (Pocillopora verrucosa, Acropora formosa, and Acropora nobilis) were studied. Samples of scleractinium coral aquaculture skeleton of A. nobilis, A. formosa, and P. verrucosa met the requirements (all study parameters) to materials for osteoplasty and 3D-scaffolds for engineering of bone tissue.

  7. State-of-the-art protein engineering approaches using biological macromolecules: A review from immobilization to implementation view point.

    Science.gov (United States)

    Bilal, Muhammad; Iqbal, Hafiz M N; Guo, Shuqi; Hu, Hongbo; Wang, Wei; Zhang, Xuehong

    2018-03-01

    Over the past years, technological and scientific advances have proven biocatalysis as a sustainable alternative than traditional chemical catalysis including organo- or metallocatalysis. In this context, immobilization based approaches represent simple but effective routes for engineering enzyme catalysts with higher activities than wild-type derivatives. Many enzymes including oxidoreductases have been engineered by rational and directed evolution, to realize the catalytic activity, enantioselectivity, and stability attributes which are essential for their biotechnological exploitation. Induce yet stable activity in enzyme catalysis offer new insights and motivation to engineer efficient catalysts for practical and commercial purposes. It has now become possible to envisage substrate accessibility to the catalytic site of the enzyme by current computational capabilities that reduce the experimental work related to the enzyme selection, screening, and engineering. Herein, state-of-the-art protein engineering approaches for improving enzymatic activities including chemical modification, directed evolution, and rational design or their combination methods are discussed. The emphasis is also given to the applications of the resulting tailored catalysts ranging from fine chemicals to novel pharmaceutical compounds that use biocatalysts as a vital step. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  9. Reversible pH-controlled DNA-binding peptide nanotweezers: An in-silico study

    Directory of Open Access Journals (Sweden)

    Gaurav Sharma

    2008-11-01

    Full Text Available Gaurav Sharma1, Kaushal Rege2,3, David E Budil4, Martin L Yarmush2,5, Constantinos Mavroidis11Department of Mechanical and Industrial Engineering; 4Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA; 2The Center for Engineering in Medicine (CEM, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 3Department of Chemical Engineering, Arizona State University, Tempe, AZ, USA; 5Department of Biomedical Engineering, Rutgers University, NJ, USAAbstract: We describe the molecular dynamics (MD-aided engineering design of mutant peptides based on the α-helical coiled-coil GCN4 leucine zipper peptide (GCN4-p1 in order to obtain environmentally-responsive nanotweezers. The actuation mechanism of the nanotweezers depends on the modification of electrostatic charges on the residues along the length of the coiled coil. Modulating the solution pH between neutral and acidic values results in the reversible movement of helices toward and away from each other and creates a complete closed-open-closed transition cycle between the helices. Our results indicate that the mutants show a reversible opening of up to 15 Å (1.5 nm; approximately 150% of the initial separation upon pH actuation. Investigation on the physicochemical phenomena that influence conformational properties, structural stability, and reversibility of the coiled-coil peptide-based nanotweezers revealed that a rationale- and design-based approach is needed to engineer stable peptide or macromolecules into stimuli-responsive devices. The efficacy of the mutant that demonstrated the most significant reversible actuation for environmentally responsive modulation of DNA-binding activity was also demonstrated. Our results have significant implications in bioseparations and in the engineering of novel transcription factors.Keywords: bionanotechnology, nanotweezers, coiled-coil, GCN4, leucine zipper, molecular dynamics, environmentally

  10. NDE in biomedical engineering

    International Nuclear Information System (INIS)

    Bhagwat, Aditya; Kumar, Pradeep

    2015-01-01

    Biomedical Engineering (BME) is an interdisciplinary field, marking the conjunction of Medical and Engineering disciplines. It combines the design and problem solving skills of engineering with medical and biological sciences to advance health care treatment, including diagnosis, monitoring, and therapy

  11. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Rice, MaryJoe K; Ruder, Warren C

    2014-01-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)

  12. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  13. An ecologically-based method for selecting ecological indicators for assessing risks to biological diversity from genetically-engineered plants

    DEFF Research Database (Denmark)

    Andow, D. A.; Lövei, Gabor L; Arpaia, Salvatore

    2013-01-01

    into ecological functional groups and selecting those that deliver the identified environmental values. (3) All of the species or ecosystem processes related to the selected functional groups are identified and (4) multi-criteria decision analysis (MCDA) is used to rank the indicator endpoint entities, which may...... adverse effects to biological diversity. The approach starts by (1) identifying the local environmental values so the ERA addresses specific concerns associated with local biological diversity. The model simplifies the indicator endpoint selection problem by (2) classifying biological diversity...... be species or ecological processes. MCDA focuses on those species and processes that are critical for the identified ecological functions and are likely to be highly exposed to the GE organism. The highest ranked indicator entities are selected for the next step. (5) Relevant risk hypotheses are identified...

  14. Manufacturing and Evaluation of a Biologically Inspired Engineered MAV Wing Compared to the Manduca Sexta Wing Under Simulated Flapping Conditions

    Science.gov (United States)

    2011-03-24

    and tested under simplified flapping conditions by analyzing ‘frozen’ digital images of the de - formed wing by methods of photogrammetry. This... Rocker System to Biological Flapping Mechanism . . . . . . . . . . . . . . 49 2.6 PhotoModeler Methods . . . . . . . . . . . . . . . . . . 55 2.7 A Word on...126 4.5.3 Residual Calculation . . . . . . . . . . . . . . . 127 4.5.4 Orientation Angle Determination (Torsional De

  15. Reversible Control of Anisotropic Electrical Conductivity using Colloidal Microfluidic Networks

    National Research Council Canada - National Science Library

    Beskok, Ali; Bevan, Michael; Lagoudas, Dimitris; Ounaies, Zoubeida; Bahukudumbi, Pradipkumar; Everett, William

    2007-01-01

    This research addresses the tunable assembly of reversible colloidal structures within microfluidic networks to engineer multifunctional materials that exhibit a wide range of electrical properties...

  16. High sensitive RNA detection by one-step RT-PCR using the genetically engineered variant of DNA polymerase with reverse transcriptase activity from hyperthermophilies.

    Science.gov (United States)

    Okano, Hiroyuki; Baba, Misato; Kawato, Katsuhiro; Hidese, Ryota; Yanagihara, Itaru; Kojima, Kenji; Takita, Teisuke; Fujiwara, Shinsuke; Yasukawa, Kiyoshi

    2018-03-01

    One-step RT-PCR has not been widely used even though some thermostable DNA polymerases with reverse transcriptase (RT) activity were developed from bacterial and archaeal polymerases, which is owing to low cDNA synthesis activity from RNA. In the present study, we developed highly-sensitive one-step RT-PCR using the single variant of family A DNA polymerase with RT activity, K4pol L329A (L329A), from the hyperthermophilic bacterium Thermotoga petrophila K4 or the 16-tuple variant of family B DNA polymerase with RT activity, RTX, from the hyperthermophilic archaeon Thermococcus kodakarensis. Optimization of reaction condition revealed that the activities for cDNA synthesis and PCR of K4pol L329A and RTX were highly affected by the concentrations of MgCl 2 and Mn(OCOCH 3 ) 2 as well as those of K4pol L329A or RTX. Under the optimized condition, 300 copies/μl of target RNA in 10 μl reaction volumes were successfully detected by the one-step RT-PCR with K4pol L329A or RTX, which was almost equally sensitive enough compared with the current RT-PCR condition using retroviral RT and thermostable DNA polymerase. Considering that K4pol L329A and RTX are stable even at 90-100°C, our results suggest that the one-step RT-PCR with K4pol L329A or RTX is more advantageous than the current one. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  17. Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

    Science.gov (United States)

    Dyment, Nathaniel A.; Lu, Yinhui; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Butler, David L.

    2015-01-01

    The prevalence of tendon and ligament injuries and inadequacies of current treatments is driving the need for alternative strategies such as tissue engineering. Fibrin and collagen biopolymers have been popular materials for creating tissue-engineered constructs (TECs), as they exhibit advantages of biocompatibility and flexibility in construct design. Unfortunately, a few studies have directly compared these materials for tendon and ligament applications. Therefore, this study aims at determining how collagen versus fibrin hydrogels affect the biological, structural, and mechanical properties of TECs during formation in vitro. Our findings show that tendon and ligament progenitor cells seeded in fibrin constructs exhibit improved tenogenic gene expression patterns compared with their collagen-based counterparts for approximately 14 days in culture. Fibrin-based constructs also exhibit improved cell-derived collagen alignment, increased linear modulus (2.2-fold greater) compared with collagen-based constructs. Cyclic tensile loading, which promotes the maturation of tendon constructs in a previous work, exhibits a material-dependent effect in this study. Fibrin constructs show trending reductions in mechanical, biological, and structural properties, whereas collagen constructs only show improved tenogenic expression in the presence of mechanical stimulation. These findings highlight that components of the mechanical stimulus (e.g., strain amplitude or time of initiation) need to be tailored to the material and cell type. Given the improvements in tenogenic expression, extracellular matrix organization, and material properties during static culture, in vitro findings presented here suggest that fibrin-based constructs may be a more suitable alternative to collagen-based constructs for tissue-engineered tendon/ligament repair. PMID:25266738

  18. Biological effects of chronic inhalation of coal mine dust and/or diesel engine exhaust in rodents

    International Nuclear Information System (INIS)

    Karagianes, M.T.; Palmer, R.F.; Stuart, B.O.; Zwicker, G.M.; Teats, D.

    1979-01-01

    Rats were killed at 4, 8, 16, and 20 mo after the start of exposures to inhaled high-CWP bituminous coal mine dust separately and combined with unscrubbed exhaust fumes from a diesel engine operated under load-rpm cycling. General health and hematologic parameters were normal. Lung lesions and accumulations of particulate matter increased with length and type of exposure; however, no animals have developed lung tumors or precancerous tissue changes up to 16 mo postexposure

  19. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Science.gov (United States)

    Nogales, Aitor; Martínez-Sobrido, Luis

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

  20. A novel genetic engineering platform for the effective management of biological contaminants for the production of microalgae

    OpenAIRE

    Loera Quesada, Maribel; Leyva González, Marco Antonio; Velázquez Juárez, Gilberto; Sánchez Calderón, Lenín; Do Nascimento, Mauro; López Arredondo, Damar; Herrera Estrella, Luis

    2017-01-01

    Microalgal cultivation that takes advantage of solar energy is one of the most cost-effective systems for the biotechnological production of biofuels, and a range of high value products, including pharmaceuticals, fertilizers and feed. However, one of the main constraints for the cultivation of microalgae is the potential contamination with biological pollutants, such as bacteria, fungi, zooplankton or other undesirable microalgae. In closed bioreactors, the control of contamination requires ...

  1. A Multidisciplinary Workshop: Self-Assembling Peptide Systems in Biology, Medicine and Engineering, Crete, Greece, July 1-6, 1999

    Science.gov (United States)

    1999-07-06

    Bombyx mori silk fibroin. Structures with polar ap -s h eets and -turns, stacking with the hydrophobic methyl groups of the alanine units in contact, are...and Science in Crete Preface The idea of organizing this workshop originated from a series of unexpected events. During a visit with Drs. Amalia...and Europe. Biology has asked some fundamental questions about nature and our own being, the origin of species, the development of living systems and

  2. Ice911 Research: A Reversible Localized Geo-Engineering Technique to Mitigate Climate Change Effects: Field Testing, Instrumentation and Climate Modeling Results

    Science.gov (United States)

    Field, L. A.; Sholtz, A.; Chetty, S.; Manzara, A.; Johnson, D.; Christodoulou, E.; Decca, R.; Walter, P.; Katuri, K.; Bhattacharyya, S.; Ivanova, D.; Mlaker, V.; Perovich, D. K.

    2017-12-01

    This work uses ecologically benign surface treatment of silica-based materials in carefully selected, limited areas to reduce polar ice melt by reflecting energy from summertime polar sun to attempt to slow ice loss due to the Ice-Albedo Feedback Effect. Application of Ice911's materials can be accomplished within a season, at a comparatively low cost, and with far less secondary environmental impact than many other proposed geo-engineering solutions. Field testing, instrumentation, safety testing, data-handling and modeling results will be presented. The albedo modification has been tested over a number of melt seasons with an evolving array of instrumentation, at multiple sites and on progressively larger scales, most recently in a small artificial pond in Minnesota and in a lake in Barrow, Alaska's BEO (Barrow Experimental Observatory) area. The test data show that the glass bubbles can provide an effective material for increasing albedo, significantly reducing the melting rate of ice. Using NCAR's CESM package the environmental impact of the approach of surface albedo modification was studied. During two separate runs, region-wide Arctic albedo modification as well as more targeted localized treatments were modeled and compared. The parameters of a surface snow layer are used as a proxy to simulate Ice911's high-albedo materials, and the modification is started in January over selected ice/snow regions in the Arctic. Preliminary results show promising possibilities of enhancements in surface albedo, sea ice area and sea-ice concentration, as well as temperature reductions of .5 to 3 degree Kelvin in the Arctic, and global average temperature reductions of .5 to 1 degrees.

  3. An Engineered Disulfide Bond Reversibly Traps the IgE-Fc3-4 in a Closed, Nonreceptor Binding Conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wurzburg, Beth A.; Kim, Beomkyu; Tarchevskaya, Svetlana S.; Eggel, Alexander; Vogel, Monique; Jardetzky, Theodore S. [Bern; (Stanford-MED)

    2013-08-02

    IgE antibodies interact with the high affinity IgE Fc receptor, FcϵRI, and activate inflammatory pathways associated with the allergic response. The IgE-Fc region, comprising the C-terminal domains of the IgE heavy chain, binds FcϵRI and can adopt different conformations ranging from a closed form incompatible with receptor binding to an open, receptor-bound state. A number of intermediate states are also observed in different IgE-Fc crystal forms. To further explore this apparent IgE-Fc conformational flexibility and to potentially trap a closed, inactive state, we generated a series of disulfide bond mutants. Here we describe the structure and biochemical properties of an IgE-Fc mutant that is trapped in the closed, non-receptor binding state via an engineered disulfide at residue 335 (Cys-335). Reduction of the disulfide at Cys-335 restores the ability of IgE-Fc to bind to its high affinity receptor, FcϵRIα. The structure of the Cys-335 mutant shows that its conformation is within the range of previously observed, closed form IgE-Fc structures and that it retains the hydrophobic pocket found in the hinge region of the closed conformation. Locking the IgE-Fc into the closed state with the Cys-335 mutation does not affect binding of two other IgE-Fc ligands, omalizumab and DARPin E2_79, demonstrating selective blocking of the high affinity receptor binding.

  4. Space Synthetic Biology (SSB)

    Data.gov (United States)

    National Aeronautics and Space Administration — This project focused on employing advanced biological engineering and bioelectrochemical reactor systems to increase life support loop closure and in situ resource...

  5. A proposal to establish an international network in molecular microbiology and genetic engineering for scientific cooperation and prevention of misuse of biological sciences in the framework of science for peace

    International Nuclear Information System (INIS)

    Becker, Y.

    1998-01-01

    The conference on 'Science and Technology for Construction of Peace' which was organized by the Landau Network Coordination Center and A. Volta Center for Scientific Culture dealt with conversion of military and technological capacities into sustainable civilian application. The ideas regarding the conversion of nuclear warheads into nuclear energy for civilian-use led to the idea that the extension of this trend of thought to molecular biology and genetic engineering, will be a useful contribution to Science for Peace. This idea of developing a Cooperation Network in Molecular Biology and Genetic Engineering that will function parallel to and with the Landau Network Coordination in the 'A. Volta' Center was discussed in the Second International Symposium on Science for Peace, Jerusalem, January 1997. It is the reason for the inclusion of the biological aspects in the deliberations of our Forum. It is hoped that the establishment of an international network in molecular biology and genetic engineering, similar to the Landau Network in physics, will support and achieve the decommissioning of biological weapons. Such a network in microbiology and genetic engineering will contribute to the elimination of biological weapons and to contributions to Science for Peace and to Culture of Peace activities of UNESCO. (author)

  6. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  7. Engineering challenges of BioNEMS: the integration of microfluidics, micro- and nanodevices, models and external control for systems biology.

    Science.gov (United States)

    Wikswo, J P; Prokop, A; Baudenbacher, F; Cliffel, D; Csukas, B; Velkovsky, M

    2006-08-01

    Systems biology, i.e. quantitative, postgenomic, postproteomic, dynamic, multiscale physiology, addresses in an integrative, quantitative manner the shockwave of genetic and proteomic information using computer models that may eventually have 10(6) dynamic variables with non-linear interactions. Historically, single biological measurements are made over minutes, suggesting the challenge of specifying 10(6) model parameters. Except for fluorescence and micro-electrode recordings, most cellular measurements have inadequate bandwidth to discern the time course of critical intracellular biochemical events. Micro-array expression profiles of thousands of genes cannot determine quantitative dynamic cellular signalling and metabolic variables. Major gaps must be bridged between the computational vision and experimental reality. The analysis of cellular signalling dynamics and control requires, first, micro- and nano-instruments that measure simultaneously multiple extracellular and intracellular variables with sufficient bandwidth; secondly, the ability to open existing internal control and signalling loops; thirdly, external BioMEMS micro-actuators that provide high bandwidth feedback and externally addressable intracellular nano-actuators; and, fourthly, real-time, closed-loop, single-cell control algorithms. The unravelling of the nested and coupled nature of cellular control loops requires simultaneous recording of multiple single-cell signatures. Externally controlled nano-actuators, needed to effect changes in the biochemical, mechanical and electrical environment both outside and inside the cell, will provide a major impetus for nanoscience.

  8. Proceedings of the 27th annual conference on engineering in medicine and biology. Volume 16. Conference held at Philadelphia, Pennsylvania, October 6--10, 1974

    International Nuclear Information System (INIS)

    Anon.

    1974-01-01

    Fifty-four sessions were held on various aspects of engineering in medicine and biology. Approximately ten papers were presented in each session and summaries of the papers are included. A paper on nuclear fueled circulatory support systems describes 238 Pu fueled blood cooled heat exchangers and implants using 241 Am, 9 Be, and 90 Sr in dogs. One dog died as a result of an extensive pulmonary neoplasm. Two sessions were devoted to cardiac pacemakers; topics included were data management systems, safety factors, implantation status of the NU-5 nuclear pacemaker, a rechargeable cardiac pacemaker system, and longevity of implantable pulse generators. A session on corporeal imaging included papers on computer processing of chest x-ray pictures, fluoroscopic image enhancement using a storage vidicon, ACTA (automatic computerized transverse axial tomographic)--the whole body scanner, and reconstruction of the image from the ACTA whole body x-ray scanner. (U.S.)

  9. Models for synthetic biology.

    Science.gov (United States)

    Kaznessis, Yiannis N

    2007-11-06

    Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

  10. Mechanical and biological properties of the micro-/nano-grain functionally graded hydroxyapatite bioceramics for bone tissue engineering.

    Science.gov (United States)

    Zhou, Changchun; Deng, Congying; Chen, Xuening; Zhao, Xiufen; Chen, Ying; Fan, Yujiang; Zhang, Xingdong

    2015-08-01

    Functionally graded materials (FGM) open the promising approach for bone tissue repair. In this study, a novel functionally graded hydroxyapatite (HA) bioceramic with micrograin and nanograin structure was fabricated. Its mechanical properties were tailored by composition of micrograin and nanograin. The dynamic mechanical analysis (DMA) indicated that the graded HA ceramics had similar mechanical property compared to natural bones. Their cytocompatibility was evaluated via fluorescent microscopy and MTT colorimetric assay. The viability and proliferation of rabbit bone marrow mesenchymal stem cells (BMSCs) on ceramics indicated that this functionally graded HA ceramic had better cytocompatibility than conventional HA ceramic. This study demonstrated that functionally graded HA ceramics create suitable structures to satisfy both the mechanical and biological requirements of bone tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Sex Reversal in Amphibians.

    Science.gov (United States)

    Flament, Stéphane

    2016-01-01

    Amphibians have been widely used to study developmental biology due to the fact that embryo development takes place independently of the maternal organism and that observations and experimental approaches are easy. Some amphibians like Xenopus became model organisms in this field. In the first part of this article, the differentiation of the gonads in amphibians and the mechanisms governing this process are reviewed. In the second part, the state of the art about sex reversal, which can be induced by steroid hormones in general and by temperature in some species, is presented. Also information about pollutants found in the environment that could interfere with the development of the amphibian reproductive apparatus or with their reproductive physiology is given. Such compounds could play a part in the amphibian decline, since in the wild, many amphibians are endangered species. © 2016 S. Karger AG, Basel.

  12. PHBV/PLLA-based composite scaffolds fabricated using an emulsion freezing/freeze-drying technique for bone tissue engineering: surface modification and in vitro biological evaluation

    International Nuclear Information System (INIS)

    Sultana, Naznin; Wang Min

    2012-01-01

    Tissue engineering combines living cells with biodegradable materials and/or bioactive components. Composite scaffolds containing biodegradable polymers and nanosized osteoconductive bioceramic with suitable properties are promising for bone tissue regeneration. In this paper, based on blending two biodegradable and biocompatible polymers, namely poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and poly(l-lactic acid) (PLLA) with incorporated nano hydroxyapatite (HA), three-dimensional composite scaffolds with controlled microstructures and an interconnected porous structure, together with high porosity, were fabricated using an emulsion freezing/freeze-drying technique. The influence of various parameters involved in the emulsion freezing/freeze-drying technique was studied for the fabrication of good-quality polymer scaffolds based on PHBV polymers. The morphology, mechanical properties and crystallinity of PHBV/PLLA and HA in PHBV/PLLA composite scaffolds and PHBV polymer scaffolds were studied. The scaffolds were coated with collagen in order to improve wettability. During in vitro biological evaluation study, it was observed that SaOS-2 cells had high attachment on collagen-coated scaffolds. Significant improvement in cell proliferation and alkaline phosphatase activity for HA-incorporated composite scaffolds was observed due to the incorporation of HA. After 3 and 7 days of culture on all scaffolds, SaOS-2 cells also had normal morphology and growth. These results indicated that PHBV/PLLA-based scaffolds fabricated via an emulsion freezing/freeze-drying technique were favorable sites for osteoblastic cells and are promising for the applications of bone tissue engineering.

  13. Radiochemistry at the University of Missouri-Columbia. A joint venture with chemistry, nuclear engineering, molecular biology, biochemistry, and the Missouri University Research Reactor (MURR)

    International Nuclear Information System (INIS)

    Miller, W.H.; Duval, P.; Jurisson, S.S.; Robertson, J.D.; Wall, J.D.; Quinn, T.P.; Volkert, W.A.; Neumeyer, G.M.

    2005-01-01

    Missouri University, a recipient of a U.S. Department of Energy Radiochemistry Education Award Program (REAP) grant in 1999, has significantly expanded its education and research mission in radiochemistry. While MU had a viable radiochemistry program through existing faculty expertise and the utilization of the Missouri University Research Reactor, the REAP award allowed MU to leverage its resources in significantly expanding capabilities in radiochemistry. Specifically, the grant enabled the: (1) hiring of a new faculty member in actinide radiochemistry (Dr. Paul Duval); (2) support of six graduate students in radiochemistry; (3) purchase of new radiochemistry laboratory equipment; (4) more extensive collaboration with DOE scientists through interactions with faculty and graduate students, and (5) revised radiochemical curriculum (joint courses across disciplines and new courses in actinide chemistry). The most significant impact of this award has been in encouraging interdisciplinary education and research. The proposal was initiated by a joint effort between Nuclear Engineering and Chemistry, but also included faculty in biochemistry, radiology, and molecular biology. Specific outcomes of the REAP grant thus far are: (1) increased educational and research capabilities in actinide chemistry (faculty hire and equipment acquisition); (2) increased integration of biochemistry and radiochemistry (e.g., radiochemical analysis of uranium speciation in biological systems); (3) stronger interdisciplinary integration of molecular biology and radiochemical sciences (alpha-emitters for treating cancer); (4) new and more extensive interactions with national laboratory facilities (e.g., student internships at LANL and LLBL, faculty and lab scientist exchange visits, analytical measurements and collaboration with the Advanced Photon Source), and (7) new research funding opportunities based on REAP partnership. (author)

  14. The contribution of biological, mathematical, clinical, engineering and social sciences to combatting the West African Ebola epidemic.

    Science.gov (United States)

    Whitty, Christopher J M

    2017-05-26

    The tragic West African Ebola epidemic claimed many lives, but would have been worse still if scientific insights from many disciplines had not been integrated to create a strong technical response. Epidemiology and modelling triggered the international response and guided where response efforts were directed; virology, engineering and clinical science helped reduce deaths and transmission in and from hospitals and treatment centres; social sciences were key to reducing deaths from funerals and in the community; diagnostic and operational research made the response more efficient; immunology and vaccine research contributed to the final stages of the epidemic and will help prevent future epidemics. These varied scientific contributions had to be integrated into a combined narrative, communicated to policymakers to inform decisions, and used by courageous local and international responders in the field in real time. Not every area of science was optimal, and in particular, clinical trials of simple interventions such as fluid management were slow to be adopted and sharing of data was initially poor. This Ebola epidemic demonstrated how science can respond to a major emergency, but also has lessons for better responses in future infectious emergencies.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'. © 2017 The Author(s).

  15. A Pressure Test to Make 10 Molecules in 90 Days: External Evaluation of Methods to Engineer Biology.

    Science.gov (United States)

    Casini, Arturo; Chang, Fang-Yuan; Eluere, Raissa; King, Andrew M; Young, Eric M; Dudley, Quentin M; Karim, Ashty; Pratt, Katelin; Bristol, Cassandra; Forget, Anthony; Ghodasara, Amar; Warden-Rothman, Robert; Gan, Rui; Cristofaro, Alexander; Borujeni, Amin Espah; Ryu, Min-Hyung; Li, Jian; Kwon, Yong-Chan; Wang, He; Tatsis, Evangelos; Rodriguez-Lopez, Carlos; O'Connor, Sarah; Medema, Marnix H; Fischbach, Michael A; Jewett, Michael C; Voigt, Christopher; Gordon, D Benjamin

    2018-03-28

    Centralized facilities for genetic engineering, or "biofoundries", offer the potential to design organisms to address emerging needs in medicine, agriculture, industry, and defense. The field has seen rapid advances in technology, but it is difficult to gauge current capabilities or identify gaps across projects. To this end, our foundry was assessed via a timed "pressure test", in which 3 months were given to build organisms to produce 10 molecules unknown to us in advance. By applying a diversity of new approaches, we produced the desired molecule or a closely related one for six out of 10 targets during the performance period and made advances toward production of the others as well. Specifically, we increased the titers of 1-hexadecanol, pyrrolnitrin, and pacidamycin D, found novel routes to the enediyne warhead underlying powerful antimicrobials, established a cell-free system for monoterpene production, produced an intermediate toward vincristine biosynthesis, and encoded 7802 individually retrievable pathways to 540 bisindoles in a DNA pool. Pathways to tetrahydrofuran and barbamide were designed and constructed, but toxicity or analytical tools inhibited further progress. In sum, we constructed 1.2 Mb DNA, built 215 strains spanning five species ( Saccharomyces cerevisiae, Escherichia coli, Streptomyces albidoflavus, Streptomyces coelicolor, and Streptomyces albovinaceus), established two cell-free systems, and performed 690 assays developed in-house for the molecules.

  16. Learning physical biology via modeling and simulation: A new course and textbook for science and engineering undergraduates

    Science.gov (United States)

    Nelson, Philip

    To a large extent, undergraduate physical-science curricula remain firmly rooted in pencil-and-paper calculation, despite the fact that most research is done with computers. To a large extent, undergraduate life-science curricula remain firmly rooted in descriptive approaches, despite the fact that much current research involves quantitative modeling. Not only does our pedagogy not reflect current reality; it also creates a spurious barrier between the fields, reinforcing the narrow silos that prevent students from connecting them. I'll describe an intermediate-level course on ``Physical Models of Living Systems.'' The prerequisite is first-year university physics and calculus. The course is a response to rapidly growing interest among undergraduates in a broad range of science and engineering majors. Students acquire several research skills that are often not addressed in traditional undergraduate courses: •Basic modeling skills; •Probabilistic modeling skills; •Data analysis methods; •Computer programming using a general-purpose platform like MATLAB or Python; •Pulling datasets from the Web for analysis; •Data visualization; •Dynamical systems, particularly feedback control. Partially supported by the NSF under Grants EF-0928048 and DMR-0832802.

  17. Tracing organizing principles: Learning from the history of systems biology

    DEFF Research Database (Denmark)

    Green, Sara; Wolkenhauer, Olaf

    2014-01-01

    on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational......With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...

  18. Preparation, characterization and biological test of 3D-scaffolds based on chitosan, fibroin and hydroxyapatite for bone tissue engineering.

    Science.gov (United States)

    Lima, Paulo Autran Leite; Resende, Cristiane Xavier; Soares, Glória Dulce de Almeida; Anselme, Karine; Almeida, Luís Eduardo

    2013-08-01

    This work describes the preparation and characterization of porous 3D-scaffolds based on chitosan (CHI), chitosan/silk fibroin (CHI/SF) and chitosan/silk fibroin/hydroxyapatite (CHI/SF/HA) by freeze drying. The biomaterials were characterized by X-ray diffraction, attenuated total reflection Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy and energy dispersive spectroscopy. In addition, studies of porosity, pore size, contact angle and biological response of SaOs-2osteoblastic cells were performed. The CHI scaffolds have a porosity of 94.2±0.9%, which is statistically higher than the one presented by CHI/SF/HA scaffolds, 89.7±2.6%. Although all scaffolds were able to promote adhesion, growth and maintenance of osteogenic differentiation of SaOs-2 cells, the new 3D-scaffold based on CHI/SF/HA showed a significantly higher cell growth at 7 days and 21 days and the level of alkaline phosphatase at 14 and 21 days was statistically superior compared to other tested materials. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Preparation, characterization and biological test of 3D-scaffolds based on chitosan, fibroin and hydroxyapatite for bone tissue engineering

    International Nuclear Information System (INIS)

    Lima, Paulo Autran Leite; Resende, Cristiane Xavier; Dulce de Almeida Soares, Glória; Anselme, Karine; Almeida, Luís Eduardo

    2013-01-01

    This work describes the preparation and characterization of porous 3D-scaffolds based on chitosan (CHI), chitosan/silk fibroin (CHI/SF) and chitosan/silk fibroin/hydroxyapatite (CHI/SF/HA) by freeze drying. The biomaterials were characterized by X-ray diffraction, attenuated total reflection Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy and energy dispersive spectroscopy. In addition, studies of porosity, pore size, contact angle and biological response of SaOs-2osteoblastic cells were performed. The CHI scaffolds have a porosity of 94.2 ± 0.9%, which is statistically higher than the one presented by CHI/SF/HA scaffolds, 89.7 ± 2.6%. Although all scaffolds were able to promote adhesion, growth and maintenance of osteogenic differentiation of SaOs-2 cells, the new 3D-scaffold based on CHI/SF/HA showed a significantly higher cell growth at 7 days and 21 days and the level of alkaline phosphatase at 14 and 21 days was statistically superior compared to other tested materials. - Highlights: • Preparation of 3D-scaffolds based on CHI, with or without addition of SF and HA. • Scaffolds exhibited interconnected porous structure (pore size superior to 50 μm). • The tripolyphosphate did not induce any significant cytotoxic response. • The CHI/SF/HA composite showed a higher cell growth and ALP activity

  20. Implantation of a novel biologic and hybridized tissue engineered bioimplant in large tendon defect: an in vivo investigation.

    Science.gov (United States)

    Oryan, Ahmad; Moshiri, Ali; Parizi, Abdolhamid Meimandi; Maffulli, Nicola

    2014-02-01

    Surgical reconstruction of large Achilles tendon defects is technically demanding. There is no standard method, and tissue engineering may be a valuable option. We investigated the effects of 3D collagen and collagen-polydioxanone sheath (PDS) implants on a large tendon defect model in rabbits. Ninety rabbits were divided into three groups: control, collagen, and collagen-PDS. In all groups, 2 cm of the left Achilles tendon were excised and discarded. A modified Kessler suture was applied to all injured tendons to retain the gap length. The control group received no graft, the treated groups were repaired using the collagen only or the collagen-PDS prostheses. The bioelectrical characteristics of the injured areas were measured at weekly intervals. The animals were euthanized at 60 days after the procedure. Gross, histopathological and ultrastructural morphology and biophysical characteristics of the injured and intact tendons were investigated. Another 90 pilot animals were also used to investigate the inflammatory response and mechanism of graft incorporation during tendon healing. The control tendons showed severe hyperemia and peritendinous adhesion, and the gastrocnemius muscle of the control animals showed severe atrophy and fibrosis, with a loose areolar connective tissue filling the injured area. The tendons receiving either collagen or collagen-PDS implants showed lower amounts of peritendinous adhesion, hyperemia and muscle atrophy, and a dense tendon filled the defect area. Compared to the control tendons, application of collagen and collagen-PDS implants significantly improved water uptake, water delivery, direct transitional electrical current and tissue resistance to direct transitional electrical current. Compared to the control tendons, both prostheses showed significantly increased diameter, density and alignment of the collagen fibrils and maturity of the tenoblasts at ultrastructure level. Both prostheses influenced favorably tendon healing

  1. Managing Reverse Logistics or Reversing Logistics Management?

    OpenAIRE

    Brito, Marisa

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

  2. Reverse Engineering in Data Integration Software

    Directory of Open Access Journals (Sweden)

    Vlad DIACONITA

    2013-05-01

    Full Text Available Integrated applications are complex solutions that help build better consolidated and standardized systems from existing (usually transactional systems. Integrated applications are complex solutions, whose complexity are determined by the economic processes they implement, the amount of data employed (millions of records grouped in hundreds of tables, databases, hundreds of GB and the number of users [11]. Oracle, once mainly known for his database and e-business solutions has been constantly expanding its product portfolio, providing solutions for SOA, BPA, Warehousing, Big Data and Cloud Computing. In this article I will review the facilities and the power of using a dedicated integration tool in an environment with multiple data sources and a target data mart.

  3. Reverse Engineering Socialbot Infiltration Strategies in Twitter

    OpenAIRE

    Freitas, Carlos A.; Benevenuto, Fabrício; Ghosh, Saptarshi; Veloso, Adriano

    2014-01-01

    Data extracted from social networks like Twitter are increasingly being used to build applications and services that mine and summarize public reactions to events, such as traffic monitoring platforms, identification of epidemic outbreaks, and public perception about people and brands. However, such services are vulnerable to attacks from socialbots $-$ automated accounts that mimic real users $-$ seeking to tamper statistics by posting messages generated automatically and interacting with le...

  4. Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications

    Energy Technology Data Exchange (ETDEWEB)

    Pon-On, Weeraphat, E-mail: fsciwpp@ku.ac.th [Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip [Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University (Thailand); Department of Physiology, Faculty of Science, Mahidol University (Thailand); Tang, I-Ming [ThEP Center, Commission of Higher Education, 328 Si Ayutthaya Rd. (Thailand); Department of Materials Science, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand)

    2014-05-01

    In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze–thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. - Graphical abstract: Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications. - Highlights: • Preparation of PVABG:ChiCol hybrid composites and their bioactivities • Mechanical

  5. Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications

    International Nuclear Information System (INIS)

    Pon-On, Weeraphat; Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Tang, I-Ming

    2014-01-01

    In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze–thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. - Graphical abstract: Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)–bioglass/chitosan–collagen composite scaffolds: A bone tissue engineering applications. - Highlights: • Preparation of PVABG:ChiCol hybrid composites and their bioactivities • Mechanical

  6. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  7. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  8. Bio Engineering Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Description/History: Chemistry and biology laboratoriesThe Bio Engineering Laboratory (BeL) is theonly full spectrum biotechnology capability within the Department...

  9. Bio-based polyurethane for tissue engineering applications: How hydroxyapatite nanoparticles influence the structure, thermal and biological behavior of polyurethane composites.

    Science.gov (United States)

    Gabriel, Laís P; Santos, Maria Elizabeth M Dos; Jardini, André L; Bastos, Gilmara N T; Dias, Carmen G B T; Webster, Thomas J; Maciel Filho, Rubens

    2017-01-01

    In this work, thermoset polyurethane composites were prepared by the addition of hydroxyapatite nanoparticles using the reactants polyol polyether and an aliphatic diisocyanate. The polyol employed in this study was extracted from the Euterpe oleracea Mart. seeds from the Amazon Region of Brazil. The influence of hydroxyapatite nanoparticles on the structure and morphology of the composites was studied using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), the structure was evaluated by Fourier transform infrared spectroscopy (FT-IR), thermal properties were analyzed by thermogravimetry analysis (TGA), and biological properties were studied by in vitro and in vivo studies. It was found that the addition of HA nanoparticles promoted fibroblast adhesion while in vivo investigations with histology confirmed that the composites promoted connective tissue adherence and did not induce inflammation. In this manner, this study supports the further investigation of bio-based, polyurethane/hydroxyapatite composites as biocompatible scaffolds for numerous tissue engineering applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Tubal Ligation Reversal

    Science.gov (United States)

    ... seal off the fallopian tubes, such as the Essure or Adiana systems, generally aren't reversible. Why ... electrocautery). Some types of sterilization, such as the Essure or Adiana systems, aren't considered reversible. Risks ...

  11. Glycosylation Engineering

    DEFF Research Database (Denmark)

    Clausen, Henrik; Wandall, Hans H.; Steentoft, Catharina

    2017-01-01

    Knowledge of the cellular pathways of glycosylation across phylogeny provides opportunities for designing glycans via genetic engineering in a wide variety of cell types including bacteria, fungi, plant cells, and mammalian cells. The commercial demand for glycosylation engineering is broad......, including production of biological therapeutics with defined glycosylation (Chapter 57). This chapter describes how knowledge of glycan structures and their metabolism (Parts I–III of this book) has led to the current state of glycosylation engineering in different cell types. Perspectives for rapid...

  12. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of

  13. Thermal Stabilization of Biologics with Photoresponsive Hydrogels.

    Science.gov (United States)

    Sridhar, Balaji V; Janczy, John R; Hatlevik, Øyvind; Wolfson, Gabriel; Anseth, Kristi S; Tibbitt, Mark W

    2018-03-12

    Modern medicine, biological research, and clinical diagnostics depend on the reliable supply and storage of complex biomolecules. However, biomolecules are inherently susceptible to thermal stress and the global distribution of value-added biologics, including vaccines, biotherapeutics, and Research Use Only (RUO) proteins, requires an integrated cold chain from point of manufacture to point of use. To mitigate reliance on the cold chain, formulations have been engineered to protect biologics from thermal stress, including materials-based strategies that impart thermal stability via direct encapsulation of the molecule. While direct encapsulation has demonstrated pronounced stabilization of proteins and complex biological fluids, no solution offers thermal stability while enabling facile and on-demand release from the encapsulating material, a critical feature for broad use. Here we show that direct encapsulation within synthetic, photoresponsive hydrogels protected biologics from thermal stress and afforded user-defined release at the point of use. The poly(ethylene glycol) (PEG)-based hydrogel was formed via a bioorthogonal, click reaction in the presence of biologics without impact on biologic activity. Cleavage of the installed photolabile moiety enabled subsequent dissolution of the network with light and release of the encapsulated biologic. Hydrogel encapsulation improved stability for encapsulated enzymes commonly used in molecular biology (β-galactosidase, alkaline phosphatase, and T4 DNA ligase) following thermal stress. β-galactosidase and alkaline phosphatase were stabilized for 4 weeks at temperatures up to 60 °C, and for 60 min at 85 °C for alkaline phosphatase. T4 DNA ligase, which loses activity rapidly at moderately elevated temperatures, was protected during thermal stress of 40 °C for 24 h and 60 °C for 30 min. These data demonstrate a general method to employ reversible polymer networks as robust excipients for thermal stability of complex

  14. Synthetic Biological Engineering of Photosynthesis

    Science.gov (United States)

    2015-11-16

    Nominee, ENI Award 2011-12 Fellow of the Radcliffe Institute for Advanced Study 2011- Elliot T. and Onie H. Adams Professorship of Biochemistry and...alternative electrofuels 2011 Nominee, ENI Award 2011-12 Fellow of the Radcliffe Institute for Advanced Study 2011- Elliot T. and Onie H

  15. Photonic engineering for biological study

    Science.gov (United States)

    Wu, Fei

    My dissertation focuses on designing and developing prototypes of optical tools in the laboratory that can facilitate practical medical therapies. More specifically, this dissertation examines two novel biophotonic techniques: (1) a frequency multiplexed confocal microscope with the potential to provide rational therapy of congestive heart failure (CHF), and (2) the "optical comb" with the potential to improve results of retina reattachment surgery and accelerate post surgical recovery. Next, I will discuss the background, design and initial experimental results of each study individually. Part I: The Frequency Multiplexed Confocal Microscope. To overcome the limitations of existing confocal microscope technology, this dissertation proposes a non-scanning, real-time, high resolution technique (a multi-point frequency multiplexed confocal microscope) to measure 3-D intracellular calcium ion concentration in a living cardiac myocyte. This method can be also applied to measure the intracellular sodium ion concentration, or other ions in which high quantum-yield fluorescent probes are available. The novelty of the proposed research lies in the introduction of carrier frequency multiplexing techniques which can differentiate fluorescence emitted at different spatial locations in cardiac myocyte by their modulated frequency. It therefore opens the possibility to visualize the transient dynamics of intracellular dynamics at multiple locations in cells simultaneously, which will shine a new light on our understanding of CHF. The procedure for frequency multiplexing proposed is described below. Multiple incident laser beams are focused onto different locations in an isolated rat cardiac myocyte with each beam modulated at a different carrier frequency. The fluorescence emission at each location therefore bears the same modulated frequency as the stimulation laser beam. Each fluorescence signal is sent to the photo multiplier tube (PMT) after being spatially filtered by a single mode fiber (functioning as a pinhole). Since each signal has a different carrier frequency, only one signal detector is required to collect multiple signal streams which eliminates the errors introduced by difference of multiple detectors. After taking the Fourier Transform of the collected data, multiple peaks can be found in the frequency domain. Each peak refers to a corresponding location in the sample. The temporal information of the fluorescence signal variation at each location can be obtained by demodulating the low frequency information from the carrier frequency, followed by an inverse Fourier transform. Part II: The "Optical Comb". Retinal detachment refers to separation of the inner layers of the retina from the underlying retinal pigment epithelium. It can cause degeneration of the retina and may lead to permanent vision loss if not promptly treated and hence is considered an ocular emergency. Currently, the only treatment available for retinal detachment is surgical reattachment. The idea of an "optical comb" is developed from the general working principle of the well known "optical tweezers" in the optical literature, which can pull micro-objects through the trapping force produced by a focused laser beam. If we can manage to incident the focused laser beam onto the misaligned photoreceptors and further scan it back and forth, trapping forces that produced may be able to "comb" the photoreceptors to be aligned, and thereby help with post surgery recovery. A series of experiments have been carried out to demonstrate the plausibility of this idea. First, several micro glass rods with size similar to human's photoreceptors (6 microns in diameter and 30 microns in length) were used. We observed that when the laser beam is focused close to one end of the micro rod originally laid on a glass coverslip, the rod is pulled to stand upright successfully, and we can manipulate the direction it faces by controlling its relative position to the laser beam. We are now experimenting with this combing technique with detached bovine retina samples to further verify its feasibility over live animal cells. (Abstract shortened by UMI.)

  16. Projeto conceitual de componentes de um forno industrial por meio da integração entre a engenharia reversa e o DFMA Conceptual design of components of an industrial oven through the integration between the reverse engineering and DFMA

    Directory of Open Access Journals (Sweden)

    Carlos Henrique Pereira Mello

    2010-01-01

    Full Text Available O tema deste artigo é o estudo da integração da engenharia reversa (ER e o projeto para manufatura e montagem (DFMA como ferramentas de suporte ao projeto conceitual de produtos. A partir de uma fundamentação teórica sobre esses conceitos, o presente trabalho visa analisar a adequação de um modelo para a utilização integrada do DFMA com a prototipagem rápida em uma abordagem de ER no projeto de um novo sistema de fechadura para forno industrial e recomendar melhorias no projeto conceitual do novo sistema de fechadura. O método de pesquisa empregado foi a pesquisa-ação, uma vez que o pesquisador buscava resolver um problema identificado dentro do objeto de estudo em parceria com a equipe de profissionais da empresa. Os resultados das recomendações para o projeto conceitual apresentam redução, especialmente, no custo, no tempo para fabricação e no tempo para montagem. Conclui-se que o modelo de integração estudado foi adequado para apoiar o processo de projeto do sistema de fechadura proposto por meio da ER.This study focuses on investigating the integration between reverse engineering (RE and design for manufacture and assembly (DFMA as tools to support the conceptual design of products. From a literature review of these concepts, this research aims to examine the adequacy of a model for the integrated use of DFMA and rapid prototyping in an ER approach in the design of a new locking system for an industrial oven and recommend improvements in conceptual design of a new lock system. The research method employed was action-research since the aim was to solve a problem identified in the company, object of study, in partnership with the company team. The results of the conceptual design indicate reductions, especially in cost, time to manufacture, and assembly time. It was concluded that the integration model studied was adequate to support the design process of the locking system proposed by the ER approach.

  17. Mechanical properties, biological activity and protein controlled release by poly(vinyl alcohol)-bioglass/chitosan-collagen composite scaffolds: a bone tissue engineering applications.

    Science.gov (United States)

    Pon-On, Weeraphat; Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip; Tang, I-Ming

    2014-05-01

    In the present study, composite scaffolds made with different weight ratios (0.5:1, 1:1 and 2:1) of bioactive glass (15Ca:80Si:5P) (BG)/polyvinyl alcohol (PVA) (PVABG) and chitosan (Chi)/collagen (Col) (ChiCol) were prepared by three mechanical freeze-thaw followed by freeze-drying to obtain the porous scaffolds. The mechanical properties and the in vitro biocompatibility of the composite scaffolds to simulated body fluid (SBF) and to rat osteoblast-like UMR-106 cells were investigated. The results from the studies indicated that the porosity and compressive strength were controlled by the weight ratio of PVABG:ChiCol. The highest compressive modulus of the composites made was 214.64 MPa which was for the 1:1 weight ratio PVABG:ChiCol. Mineralization study in SBF showed the formation of apatite crystals on the PVABG:ChiCol surface after 7 days of incubation. In vitro cell availability and proliferation tests confirmed the osteoblast attachment and growth on the PVABG:ChiCol surface. MTT and ALP tests on the 1:1 weight ratio PVABG:ChiCol composite indicated that the UMR-106 cells were viable. Alkaline phosphatase activity was found to increase with increasing culturing time. In addition, we showed the potential of PVABG:ChiCol drug delivery through PBS solution studies. 81.14% of BSA loading had been achieved and controlled release for over four weeks was observed. Our results indicated that the PVABG:ChiCol composites, especially the 1:1 weight ratio composite exhibited significantly improved mechanical, mineral deposition, biological properties and controlled release. This made them potential candidates for bone tissue engineering applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Designing synthetic biology.

    Science.gov (United States)

    Agapakis, Christina M

    2014-03-21

    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

  19. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow...... operators. Reversible flowcharts are r- Turing-complete, meaning that they can simuluate reversible Turing machines without garbage data. We also demonstrate the injectivization of classical flowcharts into reversible flowcharts. The reversible flowchart computation model provides a theoretical...

  20. Informing biological design by integration of systems and synthetic biology.

    Science.gov (United States)

    Smolke, Christina D; Silver, Pamela A

    2011-03-18

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields. Copyright © 2011 Elsevier Inc. All rights reserved.